Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Matthew J. Bown, Gregory T. Jones, Seamus C. Harrison, Benjamin J. Wright, Suzannah Bumpstead, Annette F. Baas, Solveig Gretarsdottir, Stephen A. Badger, Declan T. Bradley, Kevin Burnand, Anne H. Child, Rachel E. Clough, Gillian Cockerill, Hany Hafez, D. Julian A Scott, Simon Futers, Anne Johnson, Soroush Sohrabi, Alberto Smith, Matthew M. ThompsonFrank M. van Bockxmeer, Matthew Waltham, Stefan E. Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D. Blankensteijn, Joep A W Teijink, Cisca Wijmenga, Jacqueline de Graaf, Lambertus A. Kiemeney, Themistocles L. Assimes, Ruth McPherson, Lasse Folkersen, Anders Franco-Cereceda, Jutta Palmen, Andrew J. Smith, Nicolas Sylvius, John B. Wild, Mette Refstrup, Sarah Edkins, Rhian Gwilliam, Sarah E. Hunt, Simon Potter, Jes S. Lindholt, Ruth Frikke-Schmidt, Anne Tybjærg-Hansen, Anne E. Hughes, Jonathan Golledge, Paul E. Norman, Andre van Rij, Janet T. Powell, Per Eriksson, Kari Stefansson, John R. Thompson, Steve E. Humphries, Robert D. Sayers, Panos Deloukas, Nilesh J. Samani, Heribert Schunkert, Inke R. König, Sekar Kathiresan, Muredach P. Reilly, Themistocles L. Assimes, Hilma Holm, Michael Preuss, Alexandre F R Stewart, Maja Barbalic, Christian Gieger, Devin Absher, Zouhair Aherrahrou, Hooman Allayee, David Altshuler, Sonia S. Anand, Karl Andersen, Jeffrey L. Anderson, Diego Ardissino, Stephen G. Ball, Anthony J. Balmforth, Timothy A. Barnes, Diane M. Becker, Lewis C. Becker, Klaus Berger, Joshua C. Bis, S. Matthijs Boekholdt, Eric Boerwinkle, Peter S. Braund, Morris J. Brown, Mary Susan Burnett, Ian Buysschaert, John F. Carlquist, Li Chen, Sven Cichon, Veryan Codd, Robert W. Davies, George Dedoussis, Abbas Dehghan, Serkalem Demissie, Joseph M. Devaney, Patrick Diemert, Ron Do, Angela Doering, Sandra Eifert, Nour Eddine El Mokhtari, Stephen G. Ellis, Roberto Elosua, James C. Engert, Stephen E. Epstein, Ulf de Faire, Marcus Fischer, Aaron R. Folsom, Jennifer Freyer, Bruna Gigante, Domenico Girelli, Solveig Gretarsdottir, Vilmundur Gudnason, Jeffrey R. Gulcher, Eran Halperin, Naomi Hammond, Stanley L. Hazen, Albert Hofman, Benjamin D. Horne, Thomas Illig, Carlos Iribarren, Gregory T. Jones, J. Wouter Jukema, Michael A. Kaiser, Lee M. Kaplan, John J P Kastelein, Kay Tee Khaw, Joshua W. Knowles, Genovefa Kolovou, Augustine Kong, Reijo Laaksonen, Diether Lambrechts, Karin Leander, Guillaume Lettre, Mingyao Li, Wolfgang Lieb, Christina Loley, Andrew J. Lotery, Pier M. Mannucci, Seraya Maouche, Nicola Martinelli, Pascal P. McKeown, Christa Meisinger, Thomas Meitinger, Olle Melander, Pier Angelica Merlini, Vincent Mooser, Thomas Morgan, Thomas W. Mühleisen, Joseph B. Muhlestein, Thomas Münzel, Kiran Musunuru, Janja Nahrstaedt, Christopher P. Nelson, Markus M. Nöthen, Oliviero Olivieri, Riyaz S. Patel, Chris C. Patterson, Annette Peters, Flora Peyvandi, Liming Qu, Arshed A. Quyyumi, Daniel J. Rader, Loukianos S. Rallidis, Catherine Rice, Frits R. Rosendaal, Diana Rubin, Veikko Salomaa, M. Lourdes Sampietro, Manj S. Sandhu, Eric Schadt, Arne Schäfer, Arne Schillert, Stefan Schreiber, Jürgen Schrezenmeir, Stephen M. Schwartz, David S. Siscovick, Mohan Sivananthan, Suthesh Sivapalaratnam, Albert Smith, Tamara B. Smith, Jaapjan D. Snoep, Nicole Soranzo, John A. Spertus, Klaus Stark, Kathy Stirrups, Monika Stoll, W. H. Wilson Tang, Stephanie Tennstedt, Gudmundur Thorgeirsson, Gudmar Thorleifsson, Maciej Tomaszewski, Andre G. Uitterlinden, Andre M. van Rij, Benjamin F. Voight, Nick J. Wareham, George A. Wells, H. Erich Wichmann, Philipp S. Wild, Christina Willenborg, Jaqueline C M Witteman, Benjamin J. Wright, Shu Ye, Tanja Zeller, Andreas Ziegler, Francois Cambien, Alison H. Goodall, L. Adrienne Cupples, Thomas Quertermous, Winfried März, Christian Hengstenberg, Stefan Blankenberg, Willem H. Ouwehand, Alistair S. Hall, Panos Deloukas, John R. Thompson, Kari Stefansson, Robert Roberts, Unnur Thorsteinsdottir, Christopher J. O'Donnell, Ruth McPherson, Jeanette Erdmann, Nilesh J. Samani, Christopher Newton-Cheh, Toby Johnson, Vesela Gateva, Martin D. Tobin, Murielle Bochud, Lachlan Coin, Samer S. Najjar, Jing Hua Zhao, Simon C. Heath, Susana Eyheramendy, Konstantinos Papadakis, Benjamin F. Voight, Laura J. Scott, Feng Zhang, Martin Farrall, Toshiko Tanaka, Chris Wallace, John C. Chambers, Kay Tee Khaw, Peter Nilsson, Pim van der Harst, Silvia Polidoro, Diederick E. Grobbee, N. Charlotte Onland-Moret, Michiel L. Bots, Louise V. Wain, Katherine S. Elliott, Alexander Teumer, Jian'an Luan, Gavin Lucas, Johanna Kuusisto, Paul R. Burton, David Hadley, Wendy L. McArdle, Morris Brown, Anna Dominiczak, Stephen J. Newhouse, Nilesh J. Samani, John Webster, Eleftheria Zeggini, Jacques S. Beckmann, Sven Bergmann, Noha Lim, Kijoung Song, Peter Vollenweider, Gerard Waeber, Dawn M. Waterworth, Xin Yuan, Leif Groop, Marju Orho-Melander, Alessandra Allione, Alessandra Di Gregorio, Simonetta Guarrera, Salvatore Panico, Fulvio Ricceri, Valeria Romanazzi, Carlotta Sacerdote, Paolo Vineis, Inês Barroso, Manjinder S. Sandhu, Robert N. Luben, Gabriel J. Crawford, Pekka Jousilahti, Markus Perola, Michael Boehnke, Lori L. Bonnycastle, Francis S. Collins, Anne U. Jackson, Karen L. Mohlke, Heather M. Stringham, Timo T. Valle, Cristen J. Willer, Richard N. Bergman, Mario A. Morken, Angela Döring, Christian Gieger, Thomas Illig, Thomas Meitinger, Elin Org, Arne Pfeufer, H. Erich Wichmann, Sekar Kathiresan, Jaume Marrugat, Christopher J. O'Donnell, Stephen M. Schwartz, David S. Siscovick, Isaac Subirana, Nelson B. Freimer, Anna Liisa Hartikainen, Mark I. McCarthy, Paul F. O'Reilly, Leena Peltonen, Anneli Pouta, Paul E. de Jong, Harold Snieder, Wiek H. van Gilst, Robert Clarke, Anuj Goel, Anders Hamsten, John F. Peden, Udo Seedorf, Ann Christine Syvänen, Giovanni Tognoni, Edward G. Lakatta, Serena Sanna, Paul Scheet, David Schlessinger, Angelo Scuteri, Marcus Dörr, Florian Ernst, Stephan B. Felix, Georg Homuth, Roberto Lorbeer, Thorsten Reffelmann, Rainer Rettig, Uwe Völker, Pilar Galan, Ivo G. Gut, Serge Hercberg, G. Mark Lathrop, Diana Zelenika, Panos Deloukas, Nicole Soranzo, Frances M. Williams, Guangju Zhai, Veikko Salomaa, Markku Laakso, Roberto Elosua, Nita G. Forouhi, Henry Völzke, Cuno S. Uiterwaal, Yvonne T. van der Schouw, Mattijs E. Numans, Giuseppe Matullo, Gerjan Navis, Göran Berglund, Sheila A. Bingham, Jaspal S. Kooner, John M. Connell, Stefania Bandinelli, Luigi Ferrucci, Hugh Watkins, Tim D. Spector, Jaakko Tuomilehto, David Altshuler, David P. Strachan, Maris Laan, Pierre Meneton, Nicholas J. Wareham, Manuela Uda, Marjo Riitta Jarvelin, Vincent Mooser, Olle Melander, Ruth J F Loos, Paul Elliott, Gonçalo R. Abecasis, Mark Caulfield, Patricia B. Munroe, Benjamin F. Voight, Laura J. Scott, Valgerdur Steinthorsdottir, Andrew P. Morris, Christian Dina, Ryan P. Welch, Eleftheria Zeggini, Cornelia Huth, Yurii S. Aulchenko, Gudmar Thorleifsson, Laura J. McCulloch, Teresa Ferreira, Harald Grallert, Najaf Amin, Guanming Wu, Cristen J. Willer, Soumya Raychaudhuri, Steve A. McCarroll, Claudia Langenberg, Oliver M. Hofmann, Josée Dupuis, Lu Qi, Ayellet V. Segrè, Mandy van Hoek, Pau Navarro, Kristin Ardlie, Beverley Balkau, Rafn Benediktsson, Amanda J. Bennett, Roza Blagieva, Eric Boerwinkle, Lori L. Bonnycastle, Kristina Bengtsson Boström, Bert Bravenboer, Suzannah Bumpstead, Noël P. Burtt, Guillaume Charpentier, Peter S. Chines, Marilyn Cornelis, David J. Couper, Gabe Crawford, Alex S F Doney, Katherine S. Elliott, Amanda L. Elliott, Michael R. Erdos, Caroline S. Fox, Christopher S. Franklin, Martha Ganser, Christian Gieger, Niels Grarup, Todd Green, Simon Griffin, Christopher J. Groves, Candace Guiducci, Samy Hadjadj, Neelam Hassanali, Christian Herder, Bo Isomaa, Anne U. Jackson, Paul R V Johnson, Torben Jørgensen, Wen H L Kao, Norman Klopp, Augustine Kong, Peter Kraft, Torsten Lauritzen, Man Li, Aloysius Lieverse, Cecilia M. Lindgren, Valeriya Lyssenko, Michel Marre, Thomas Meitinger, Kristian Midthjell, Mario A. Morken, Narisu Narisu, Peter Nilsson, Katharine R. Owen, Felicity Payne, John R B Perry, Ann Kristin Petersen, Carl Platou, Christine Proença, Inga Prokopenko, Wolfgang Rathmann, N. William Rayner, Neil R. Robertson, Ghislain Rocheleau, Michael Roden, Michael J. Sampson, Richa Saxena, Beverley M. Shields, Peter Shrader, Gunnar Sigurdsson, Thomas Sparsø, Klaus Strassburger, Heather M. Stringham, Qi Sun, Amy J. Swift, Barbara Thorand, Jean Tichet, Tiinamaija Tuomi, Rob M. van Dam, Timon W. van Haeften, Thijs van Herpt, Jana V. van Vliet-Ostaptchouk, G. Bragi Walters, Michael N. Weedon, Cisca Wijmenga, Jacqueline Witteman, Richard N. Bergman, Stephane Cauchi, Francis S. Collins, Anna L. Gloyn, Ulf Gyllensten, Torben Hansen, Winston A. Hide, Graham A. Hitman, Albert Hofman, David J. Hunter, Kristian Hveem, Markku Laakso, Karen L. Mohlke, Andrew D. Morris, Colin N A Palmer, Peter P. Pramstaller, Igor Rudan, Eric Sijbrands, Lincoln D. Stein, Jaakko Tuomilehto, Andre Uitterlinden, Mark Walker, Nicholas J. Wareham, Richard M. Watanabe, Goncalo R. Abecasis, Bernhard O. Boehm, Harry Campbell, Mark J. Daly, Andrew T. Hattersley, Frank B. Hu, James B. Meigs, James S. Pankow, Oluf Pedersen, H. Erich Wichmann, Inês Barroso, Jose C. Florez, Timothy M. Frayling, Leif Groop, Rob Sladek, Unnur Thorsteinsdottir, James F. Wilson, Thomas Illig, Philippe Froguel, Cornelia M. van Duijn, Kari Stefansson, David Altshuler, Michael Boehnke, Mark I. McCarthy, Ross D. Blair, Andrew A. Hill, B. Gerry Hill, David R. Lewis, Les A. McNoe, Tony R. Merriman, Dilip K. Naik, L. Vicky Phillips, Ian A. Thomson, Ruth Topless, Thodur M. Vasudevan, Grace Yu

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value <1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p <1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Original languageEnglish
Pages (from-to)619-627
Number of pages9
JournalAmerican Journal of Human Genetics
Volume89
Issue number5
DOIs
Publication statusPublished - Nov 11 2011

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-1
Abdominal Aortic Aneurysm
Lipoprotein Receptors
Homozygote
Single Nucleotide Polymorphism
Adventitia
Proteins
Genome-Wide Association Study
Hyperlipidemias
Introns
Coronary Artery Disease
Odds Ratio
Binding Sites
Genotype
Blood Pressure
Morbidity
Gene Expression
Mortality

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bown, M. J., Jones, G. T., Harrison, S. C., Wright, B. J., Bumpstead, S., Baas, A. F., ... Yu, G. (2011). Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. American Journal of Human Genetics, 89(5), 619-627. https://doi.org/10.1016/j.ajhg.2011.10.002

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. / Bown, Matthew J.; Jones, Gregory T.; Harrison, Seamus C.; Wright, Benjamin J.; Bumpstead, Suzannah; Baas, Annette F.; Gretarsdottir, Solveig; Badger, Stephen A.; Bradley, Declan T.; Burnand, Kevin; Child, Anne H.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A; Futers, Simon; Johnson, Anne; Sohrabi, Soroush; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Waltham, Matthew; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A W; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Assimes, Themistocles L.; McPherson, Ruth; Folkersen, Lasse; Franco-Cereceda, Anders; Palmen, Jutta; Smith, Andrew J.; Sylvius, Nicolas; Wild, John B.; Refstrup, Mette; Edkins, Sarah; Gwilliam, Rhian; Hunt, Sarah E.; Potter, Simon; Lindholt, Jes S.; Frikke-Schmidt, Ruth; Tybjærg-Hansen, Anne; Hughes, Anne E.; Golledge, Jonathan; Norman, Paul E.; van Rij, Andre; Powell, Janet T.; Eriksson, Per; Stefansson, Kari; Thompson, John R.; Humphries, Steve E.; Sayers, Robert D.; Deloukas, Panos; Samani, Nilesh J.; Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F R; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Matthijs Boekholdt, S.; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Susan Burnett, Mary; Buysschaert, Ian; Carlquist, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Diemert, Patrick; Do, Ron; Doering, Angela; Eifert, Sandra; El Mokhtari, Nour Eddine; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; de Faire, Ulf; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Wouter Jukema, J.; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J P; Khaw, Kay Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Angelica Merlini, Pier; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Lourdes Sampietro, M.; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Wilson Tang, W. H.; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H. Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C M; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Adrienne Cupples, L.; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O'Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.; Newton-Cheh, Christopher; Johnson, Toby; Gateva, Vesela; Tobin, Martin D.; Bochud, Murielle; Coin, Lachlan; Najjar, Samer S.; Hua Zhao, Jing; Heath, Simon C.; Eyheramendy, Susana; Papadakis, Konstantinos; Voight, Benjamin F.; Scott, Laura J.; Zhang, Feng; Farrall, Martin; Tanaka, Toshiko; Wallace, Chris; Chambers, John C.; Khaw, Kay Tee; Nilsson, Peter; van der Harst, Pim; Polidoro, Silvia; Grobbee, Diederick E.; Onland-Moret, N. Charlotte; Bots, Michiel L.; Wain, Louise V.; Elliott, Katherine S.; Teumer, Alexander; Luan, Jian'an; Lucas, Gavin; Kuusisto, Johanna; Burton, Paul R.; Hadley, David; McArdle, Wendy L.; Brown, Morris; Dominiczak, Anna; Newhouse, Stephen J.; Samani, Nilesh J.; Webster, John; Zeggini, Eleftheria; Beckmann, Jacques S.; Bergmann, Sven; Lim, Noha; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M.; Yuan, Xin; Groop, Leif; Orho-Melander, Marju; Allione, Alessandra; Di Gregorio, Alessandra; Guarrera, Simonetta; Panico, Salvatore; Ricceri, Fulvio; Romanazzi, Valeria; Sacerdote, Carlotta; Vineis, Paolo; Barroso, Inês; Sandhu, Manjinder S.; Luben, Robert N.; Crawford, Gabriel J.; Jousilahti, Pekka; Perola, Markus; Boehnke, Michael; Bonnycastle, Lori L.; Collins, Francis S.; Jackson, Anne U.; Mohlke, Karen L.; Stringham, Heather M.; Valle, Timo T.; Willer, Cristen J.; Bergman, Richard N.; Morken, Mario A.; Döring, Angela; Gieger, Christian; Illig, Thomas; Meitinger, Thomas; Org, Elin; Pfeufer, Arne; Wichmann, H. Erich; Kathiresan, Sekar; Marrugat, Jaume; O'Donnell, Christopher J.; Schwartz, Stephen M.; Siscovick, David S.; Subirana, Isaac; Freimer, Nelson B.; Hartikainen, Anna Liisa; McCarthy, Mark I.; O'Reilly, Paul F.; Peltonen, Leena; Pouta, Anneli; de Jong, Paul E.; Snieder, Harold; van Gilst, Wiek H.; Clarke, Robert; Goel, Anuj; Hamsten, Anders; Peden, John F.; Seedorf, Udo; Syvänen, Ann Christine; Tognoni, Giovanni; Lakatta, Edward G.; Sanna, Serena; Scheet, Paul; Schlessinger, David; Scuteri, Angelo; Dörr, Marcus; Ernst, Florian; Felix, Stephan B.; Homuth, Georg; Lorbeer, Roberto; Reffelmann, Thorsten; Rettig, Rainer; Völker, Uwe; Galan, Pilar; Gut, Ivo G.; Hercberg, Serge; Mark Lathrop, G.; Zelenika, Diana; Deloukas, Panos; Soranzo, Nicole; Williams, Frances M.; Zhai, Guangju; Salomaa, Veikko; Laakso, Markku; Elosua, Roberto; Forouhi, Nita G.; Völzke, Henry; Uiterwaal, Cuno S.; van der Schouw, Yvonne T.; Numans, Mattijs E.; Matullo, Giuseppe; Navis, Gerjan; Berglund, Göran; Bingham, Sheila A.; Kooner, Jaspal S.; Connell, John M.; Bandinelli, Stefania; Ferrucci, Luigi; Watkins, Hugh; Spector, Tim D.; Tuomilehto, Jaakko; Altshuler, David; Strachan, David P.; Laan, Maris; Meneton, Pierre; Wareham, Nicholas J.; Uda, Manuela; Jarvelin, Marjo Riitta; Mooser, Vincent; Melander, Olle; Loos, Ruth J F; Elliott, Paul; Abecasis, Gonçalo R.; Caulfield, Mark; Munroe, Patricia B.; Voight, Benjamin F.; Scott, Laura J.; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Dina, Christian; Welch, Ryan P.; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S.; Thorleifsson, Gudmar; McCulloch, Laura J.; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J.; Raychaudhuri, Soumya; McCarroll, Steve A.; Langenberg, Claudia; Hofmann, Oliver M.; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V.; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J.; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L.; Bengtsson Boström, Kristina; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P.; Charpentier, Guillaume; Chines, Peter S.; Cornelis, Marilyn; Couper, David J.; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S.; Elliott, Amanda L.; Erdos, Michael R.; Fox, Caroline S.; Franklin, Christopher S.; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J.; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U.; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M.; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A.; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R.; Payne, Felicity; Perry, John R B; Petersen, Ann Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; William Rayner, N.; Robertson, Neil R.; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J.; Saxena, Richa; Shields, Beverley M.; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M.; Sun, Qi; Swift, Amy J.; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M.; van Haeften, Timon W.; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V.; Bragi Walters, G.; Weedon, Michael N.; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N.; Cauchi, Stephane; Collins, Francis S.; Gloyn, Anna L.; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A.; Hitman, Graham A.; Hofman, Albert; Hunter, David J.; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L.; Morris, Andrew D.; Palmer, Colin N A; Pramstaller, Peter P.; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D.; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J.; Watanabe, Richard M.; Abecasis, Goncalo R.; Boehm, Bernhard O.; Campbell, Harry; Daly, Mark J.; Hattersley, Andrew T.; Hu, Frank B.; Meigs, James B.; Pankow, James S.; Pedersen, Oluf; Wichmann, H. Erich; Barroso, Inês; Florez, Jose C.; Frayling, Timothy M.; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F.; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M.; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I.; Blair, Ross D.; Hill, Andrew A.; Gerry Hill, B.; Lewis, David R.; McNoe, Les A.; Merriman, Tony R.; Naik, Dilip K.; Vicky Phillips, L.; Thomson, Ian A.; Topless, Ruth; Vasudevan, Thodur M.; Yu, Grace.

In: American Journal of Human Genetics, Vol. 89, No. 5, 11.11.2011, p. 619-627.

Research output: Contribution to journalArticle

Bown, MJ, Jones, GT, Harrison, SC, Wright, BJ, Bumpstead, S, Baas, AF, Gretarsdottir, S, Badger, SA, Bradley, DT, Burnand, K, Child, AH, Clough, RE, Cockerill, G, Hafez, H, Scott, DJA, Futers, S, Johnson, A, Sohrabi, S, Smith, A, Thompson, MM, van Bockxmeer, FM, Waltham, M, Matthiasson, SE, Thorleifsson, G, Thorsteinsdottir, U, Blankensteijn, JD, Teijink, JAW, Wijmenga, C, de Graaf, J, Kiemeney, LA, Assimes, TL, McPherson, R, Folkersen, L, Franco-Cereceda, A, Palmen, J, Smith, AJ, Sylvius, N, Wild, JB, Refstrup, M, Edkins, S, Gwilliam, R, Hunt, SE, Potter, S, Lindholt, JS, Frikke-Schmidt, R, Tybjærg-Hansen, A, Hughes, AE, Golledge, J, Norman, PE, van Rij, A, Powell, JT, Eriksson, P, Stefansson, K, Thompson, JR, Humphries, SE, Sayers, RD, Deloukas, P, Samani, NJ, Schunkert, H, König, IR, Kathiresan, S, Reilly, MP, Assimes, TL, Holm, H, Preuss, M, Stewart, AFR, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, SS, Andersen, K, Anderson, JL, Ardissino, D, Ball, SG, Balmforth, AJ, Barnes, TA, Becker, DM, Becker, LC, Berger, K, Bis, JC, Matthijs Boekholdt, S, Boerwinkle, E, Braund, PS, Brown, MJ, Susan Burnett, M, Buysschaert, I, Carlquist, JF, Chen, L, Cichon, S, Codd, V, Davies, RW, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, JM, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari, NE, Ellis, SG, Elosua, R, Engert, JC, Epstein, SE, de Faire, U, Fischer, M, Folsom, AR, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, JR, Halperin, E, Hammond, N, Hazen, SL, Hofman, A, Horne, BD, Illig, T, Iribarren, C, Jones, GT, Wouter Jukema, J, Kaiser, MA, Kaplan, LM, Kastelein, JJP, Khaw, KT, Knowles, JW, Kolovou, G, Kong, A, Laaksonen, R, Lambrechts, D, Leander, K, Lettre, G, Li, M, Lieb, W, Loley, C, Lotery, AJ, Mannucci, PM, Maouche, S, Martinelli, N, McKeown, PP, Meisinger, C, Meitinger, T, Melander, O, Angelica Merlini, P, Mooser, V, Morgan, T, Mühleisen, TW, Muhlestein, JB, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, CP, Nöthen, MM, Olivieri, O, Patel, RS, Patterson, CC, Peters, A, Peyvandi, F, Qu, L, Quyyumi, AA, Rader, DJ, Rallidis, LS, Rice, C, Rosendaal, FR, Rubin, D, Salomaa, V, Lourdes Sampietro, M, Sandhu, MS, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, SM, Siscovick, DS, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, TB, Snoep, JD, Soranzo, N, Spertus, JA, Stark, K, Stirrups, K, Stoll, M, Wilson Tang, WH, Tennstedt, S, Thorgeirsson, G, Thorleifsson, G, Tomaszewski, M, Uitterlinden, AG, van Rij, AM, Voight, BF, Wareham, NJ, Wells, GA, Wichmann, HE, Wild, PS, Willenborg, C, Witteman, JCM, Wright, BJ, Ye, S, Zeller, T, Ziegler, A, Cambien, F, Goodall, AH, Adrienne Cupples, L, Quertermous, T, März, W, Hengstenberg, C, Blankenberg, S, Ouwehand, WH, Hall, AS, Deloukas, P, Thompson, JR, Stefansson, K, Roberts, R, Thorsteinsdottir, U, O'Donnell, CJ, McPherson, R, Erdmann, J, Samani, NJ, Newton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Hua Zhao, J, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, KT, Nilsson, P, van der Harst, P, Polidoro, S, Grobbee, DE, Onland-Moret, NC, Bots, ML, Wain, LV, Elliott, KS, Teumer, A, Luan, J, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, Brown, M, Dominiczak, A, Newhouse, SJ, Samani, NJ, Webster, J, Zeggini, E, Beckmann, JS, Bergmann, S, Lim, N, Song, K, Vollenweider, P, Waeber, G, Waterworth, DM, Yuan, X, Groop, L, Orho-Melander, M, Allione, A, Di Gregorio, A, Guarrera, S, Panico, S, Ricceri, F, Romanazzi, V, Sacerdote, C, Vineis, P, Barroso, I, Sandhu, MS, Luben, RN, Crawford, GJ, Jousilahti, P, Perola, M, Boehnke, M, Bonnycastle, LL, Collins, FS, Jackson, AU, Mohlke, KL, Stringham, HM, Valle, TT, Willer, CJ, Bergman, RN, Morken, MA, Döring, A, Gieger, C, Illig, T, Meitinger, T, Org, E, Pfeufer, A, Wichmann, HE, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, AL, McCarthy, MI, O'Reilly, PF, Peltonen, L, Pouta, A, de Jong, PE, Snieder, H, van Gilst, WH, Clarke, R, Goel, A, Hamsten, A, Peden, JF, Seedorf, U, Syvänen, AC, Tognoni, G, Lakatta, EG, Sanna, S, Scheet, P, Schlessinger, D, Scuteri, A, Dörr, M, Ernst, F, Felix, SB, Homuth, G, Lorbeer, R, Reffelmann, T, Rettig, R, Völker, U, Galan, P, Gut, IG, Hercberg, S, Mark Lathrop, G, Zelenika, D, Deloukas, P, Soranzo, N, Williams, FM, Zhai, G, Salomaa, V, Laakso, M, Elosua, R, Forouhi, NG, Völzke, H, Uiterwaal, CS, van der Schouw, YT, Numans, ME, Matullo, G, Navis, G, Berglund, G, Bingham, SA, Kooner, JS, Connell, JM, Bandinelli, S, Ferrucci, L, Watkins, H, Spector, TD, Tuomilehto, J, Altshuler, D, Strachan, DP, Laan, M, Meneton, P, Wareham, NJ, Uda, M, Jarvelin, MR, Mooser, V, Melander, O, Loos, RJF, Elliott, P, Abecasis, GR, Caulfield, M, Munroe, PB, Voight, BF, Scott, LJ, Steinthorsdottir, V, Morris, AP, Dina, C, Welch, RP, Zeggini, E, Huth, C, Aulchenko, YS, Thorleifsson, G, McCulloch, LJ, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, CJ, Raychaudhuri, S, McCarroll, SA, Langenberg, C, Hofmann, OM, Dupuis, J, Qi, L, Segrè, AV, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, AJ, Blagieva, R, Boerwinkle, E, Bonnycastle, LL, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, NP, Charpentier, G, Chines, PS, Cornelis, M, Couper, DJ, Crawford, G, Doney, ASF, Elliott, KS, Elliott, AL, Erdos, MR, Fox, CS, Franklin, CS, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, CJ, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, AU, Johnson, PRV, Jørgensen, T, Kao, WHL, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, CM, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, MA, Narisu, N, Nilsson, P, Owen, KR, Payne, F, Perry, JRB, Petersen, AK, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, William Rayner, N, Robertson, NR, Rocheleau, G, Roden, M, Sampson, MJ, Saxena, R, Shields, BM, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, HM, Sun, Q, Swift, AJ, Thorand, B, Tichet, J, Tuomi, T, van Dam, RM, van Haeften, TW, van Herpt, T, van Vliet-Ostaptchouk, JV, Bragi Walters, G, Weedon, MN, Wijmenga, C, Witteman, J, Bergman, RN, Cauchi, S, Collins, FS, Gloyn, AL, Gyllensten, U, Hansen, T, Hide, WA, Hitman, GA, Hofman, A, Hunter, DJ, Hveem, K, Laakso, M, Mohlke, KL, Morris, AD, Palmer, CNA, Pramstaller, PP, Rudan, I, Sijbrands, E, Stein, LD, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, NJ, Watanabe, RM, Abecasis, GR, Boehm, BO, Campbell, H, Daly, MJ, Hattersley, AT, Hu, FB, Meigs, JB, Pankow, JS, Pedersen, O, Wichmann, HE, Barroso, I, Florez, JC, Frayling, TM, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, JF, Illig, T, Froguel, P, van Duijn, CM, Stefansson, K, Altshuler, D, Boehnke, M, McCarthy, MI, Blair, RD, Hill, AA, Gerry Hill, B, Lewis, DR, McNoe, LA, Merriman, TR, Naik, DK, Vicky Phillips, L, Thomson, IA, Topless, R, Vasudevan, TM & Yu, G 2011, 'Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1', American Journal of Human Genetics, vol. 89, no. 5, pp. 619-627. https://doi.org/10.1016/j.ajhg.2011.10.002
Bown, Matthew J. ; Jones, Gregory T. ; Harrison, Seamus C. ; Wright, Benjamin J. ; Bumpstead, Suzannah ; Baas, Annette F. ; Gretarsdottir, Solveig ; Badger, Stephen A. ; Bradley, Declan T. ; Burnand, Kevin ; Child, Anne H. ; Clough, Rachel E. ; Cockerill, Gillian ; Hafez, Hany ; Scott, D. Julian A ; Futers, Simon ; Johnson, Anne ; Sohrabi, Soroush ; Smith, Alberto ; Thompson, Matthew M. ; van Bockxmeer, Frank M. ; Waltham, Matthew ; Matthiasson, Stefan E. ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Blankensteijn, Jan D. ; Teijink, Joep A W ; Wijmenga, Cisca ; de Graaf, Jacqueline ; Kiemeney, Lambertus A. ; Assimes, Themistocles L. ; McPherson, Ruth ; Folkersen, Lasse ; Franco-Cereceda, Anders ; Palmen, Jutta ; Smith, Andrew J. ; Sylvius, Nicolas ; Wild, John B. ; Refstrup, Mette ; Edkins, Sarah ; Gwilliam, Rhian ; Hunt, Sarah E. ; Potter, Simon ; Lindholt, Jes S. ; Frikke-Schmidt, Ruth ; Tybjærg-Hansen, Anne ; Hughes, Anne E. ; Golledge, Jonathan ; Norman, Paul E. ; van Rij, Andre ; Powell, Janet T. ; Eriksson, Per ; Stefansson, Kari ; Thompson, John R. ; Humphries, Steve E. ; Sayers, Robert D. ; Deloukas, Panos ; Samani, Nilesh J. ; Schunkert, Heribert ; König, Inke R. ; Kathiresan, Sekar ; Reilly, Muredach P. ; Assimes, Themistocles L. ; Holm, Hilma ; Preuss, Michael ; Stewart, Alexandre F R ; Barbalic, Maja ; Gieger, Christian ; Absher, Devin ; Aherrahrou, Zouhair ; Allayee, Hooman ; Altshuler, David ; Anand, Sonia S. ; Andersen, Karl ; Anderson, Jeffrey L. ; Ardissino, Diego ; Ball, Stephen G. ; Balmforth, Anthony J. ; Barnes, Timothy A. ; Becker, Diane M. ; Becker, Lewis C. ; Berger, Klaus ; Bis, Joshua C. ; Matthijs Boekholdt, S. ; Boerwinkle, Eric ; Braund, Peter S. ; Brown, Morris J. ; Susan Burnett, Mary ; Buysschaert, Ian ; Carlquist, John F. ; Chen, Li ; Cichon, Sven ; Codd, Veryan ; Davies, Robert W. ; Dedoussis, George ; Dehghan, Abbas ; Demissie, Serkalem ; Devaney, Joseph M. ; Diemert, Patrick ; Do, Ron ; Doering, Angela ; Eifert, Sandra ; El Mokhtari, Nour Eddine ; Ellis, Stephen G. ; Elosua, Roberto ; Engert, James C. ; Epstein, Stephen E. ; de Faire, Ulf ; Fischer, Marcus ; Folsom, Aaron R. ; Freyer, Jennifer ; Gigante, Bruna ; Girelli, Domenico ; Gretarsdottir, Solveig ; Gudnason, Vilmundur ; Gulcher, Jeffrey R. ; Halperin, Eran ; Hammond, Naomi ; Hazen, Stanley L. ; Hofman, Albert ; Horne, Benjamin D. ; Illig, Thomas ; Iribarren, Carlos ; Jones, Gregory T. ; Wouter Jukema, J. ; Kaiser, Michael A. ; Kaplan, Lee M. ; Kastelein, John J P ; Khaw, Kay Tee ; Knowles, Joshua W. ; Kolovou, Genovefa ; Kong, Augustine ; Laaksonen, Reijo ; Lambrechts, Diether ; Leander, Karin ; Lettre, Guillaume ; Li, Mingyao ; Lieb, Wolfgang ; Loley, Christina ; Lotery, Andrew J. ; Mannucci, Pier M. ; Maouche, Seraya ; Martinelli, Nicola ; McKeown, Pascal P. ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Angelica Merlini, Pier ; Mooser, Vincent ; Morgan, Thomas ; Mühleisen, Thomas W. ; Muhlestein, Joseph B. ; Münzel, Thomas ; Musunuru, Kiran ; Nahrstaedt, Janja ; Nelson, Christopher P. ; Nöthen, Markus M. ; Olivieri, Oliviero ; Patel, Riyaz S. ; Patterson, Chris C. ; Peters, Annette ; Peyvandi, Flora ; Qu, Liming ; Quyyumi, Arshed A. ; Rader, Daniel J. ; Rallidis, Loukianos S. ; Rice, Catherine ; Rosendaal, Frits R. ; Rubin, Diana ; Salomaa, Veikko ; Lourdes Sampietro, M. ; Sandhu, Manj S. ; Schadt, Eric ; Schäfer, Arne ; Schillert, Arne ; Schreiber, Stefan ; Schrezenmeir, Jürgen ; Schwartz, Stephen M. ; Siscovick, David S. ; Sivananthan, Mohan ; Sivapalaratnam, Suthesh ; Smith, Albert ; Smith, Tamara B. ; Snoep, Jaapjan D. ; Soranzo, Nicole ; Spertus, John A. ; Stark, Klaus ; Stirrups, Kathy ; Stoll, Monika ; Wilson Tang, W. H. ; Tennstedt, Stephanie ; Thorgeirsson, Gudmundur ; Thorleifsson, Gudmar ; Tomaszewski, Maciej ; Uitterlinden, Andre G. ; van Rij, Andre M. ; Voight, Benjamin F. ; Wareham, Nick J. ; Wells, George A. ; Wichmann, H. Erich ; Wild, Philipp S. ; Willenborg, Christina ; Witteman, Jaqueline C M ; Wright, Benjamin J. ; Ye, Shu ; Zeller, Tanja ; Ziegler, Andreas ; Cambien, Francois ; Goodall, Alison H. ; Adrienne Cupples, L. ; Quertermous, Thomas ; März, Winfried ; Hengstenberg, Christian ; Blankenberg, Stefan ; Ouwehand, Willem H. ; Hall, Alistair S. ; Deloukas, Panos ; Thompson, John R. ; Stefansson, Kari ; Roberts, Robert ; Thorsteinsdottir, Unnur ; O'Donnell, Christopher J. ; McPherson, Ruth ; Erdmann, Jeanette ; Samani, Nilesh J. ; Newton-Cheh, Christopher ; Johnson, Toby ; Gateva, Vesela ; Tobin, Martin D. ; Bochud, Murielle ; Coin, Lachlan ; Najjar, Samer S. ; Hua Zhao, Jing ; Heath, Simon C. ; Eyheramendy, Susana ; Papadakis, Konstantinos ; Voight, Benjamin F. ; Scott, Laura J. ; Zhang, Feng ; Farrall, Martin ; Tanaka, Toshiko ; Wallace, Chris ; Chambers, John C. ; Khaw, Kay Tee ; Nilsson, Peter ; van der Harst, Pim ; Polidoro, Silvia ; Grobbee, Diederick E. ; Onland-Moret, N. Charlotte ; Bots, Michiel L. ; Wain, Louise V. ; Elliott, Katherine S. ; Teumer, Alexander ; Luan, Jian'an ; Lucas, Gavin ; Kuusisto, Johanna ; Burton, Paul R. ; Hadley, David ; McArdle, Wendy L. ; Brown, Morris ; Dominiczak, Anna ; Newhouse, Stephen J. ; Samani, Nilesh J. ; Webster, John ; Zeggini, Eleftheria ; Beckmann, Jacques S. ; Bergmann, Sven ; Lim, Noha ; Song, Kijoung ; Vollenweider, Peter ; Waeber, Gerard ; Waterworth, Dawn M. ; Yuan, Xin ; Groop, Leif ; Orho-Melander, Marju ; Allione, Alessandra ; Di Gregorio, Alessandra ; Guarrera, Simonetta ; Panico, Salvatore ; Ricceri, Fulvio ; Romanazzi, Valeria ; Sacerdote, Carlotta ; Vineis, Paolo ; Barroso, Inês ; Sandhu, Manjinder S. ; Luben, Robert N. ; Crawford, Gabriel J. ; Jousilahti, Pekka ; Perola, Markus ; Boehnke, Michael ; Bonnycastle, Lori L. ; Collins, Francis S. ; Jackson, Anne U. ; Mohlke, Karen L. ; Stringham, Heather M. ; Valle, Timo T. ; Willer, Cristen J. ; Bergman, Richard N. ; Morken, Mario A. ; Döring, Angela ; Gieger, Christian ; Illig, Thomas ; Meitinger, Thomas ; Org, Elin ; Pfeufer, Arne ; Wichmann, H. Erich ; Kathiresan, Sekar ; Marrugat, Jaume ; O'Donnell, Christopher J. ; Schwartz, Stephen M. ; Siscovick, David S. ; Subirana, Isaac ; Freimer, Nelson B. ; Hartikainen, Anna Liisa ; McCarthy, Mark I. ; O'Reilly, Paul F. ; Peltonen, Leena ; Pouta, Anneli ; de Jong, Paul E. ; Snieder, Harold ; van Gilst, Wiek H. ; Clarke, Robert ; Goel, Anuj ; Hamsten, Anders ; Peden, John F. ; Seedorf, Udo ; Syvänen, Ann Christine ; Tognoni, Giovanni ; Lakatta, Edward G. ; Sanna, Serena ; Scheet, Paul ; Schlessinger, David ; Scuteri, Angelo ; Dörr, Marcus ; Ernst, Florian ; Felix, Stephan B. ; Homuth, Georg ; Lorbeer, Roberto ; Reffelmann, Thorsten ; Rettig, Rainer ; Völker, Uwe ; Galan, Pilar ; Gut, Ivo G. ; Hercberg, Serge ; Mark Lathrop, G. ; Zelenika, Diana ; Deloukas, Panos ; Soranzo, Nicole ; Williams, Frances M. ; Zhai, Guangju ; Salomaa, Veikko ; Laakso, Markku ; Elosua, Roberto ; Forouhi, Nita G. ; Völzke, Henry ; Uiterwaal, Cuno S. ; van der Schouw, Yvonne T. ; Numans, Mattijs E. ; Matullo, Giuseppe ; Navis, Gerjan ; Berglund, Göran ; Bingham, Sheila A. ; Kooner, Jaspal S. ; Connell, John M. ; Bandinelli, Stefania ; Ferrucci, Luigi ; Watkins, Hugh ; Spector, Tim D. ; Tuomilehto, Jaakko ; Altshuler, David ; Strachan, David P. ; Laan, Maris ; Meneton, Pierre ; Wareham, Nicholas J. ; Uda, Manuela ; Jarvelin, Marjo Riitta ; Mooser, Vincent ; Melander, Olle ; Loos, Ruth J F ; Elliott, Paul ; Abecasis, Gonçalo R. ; Caulfield, Mark ; Munroe, Patricia B. ; Voight, Benjamin F. ; Scott, Laura J. ; Steinthorsdottir, Valgerdur ; Morris, Andrew P. ; Dina, Christian ; Welch, Ryan P. ; Zeggini, Eleftheria ; Huth, Cornelia ; Aulchenko, Yurii S. ; Thorleifsson, Gudmar ; McCulloch, Laura J. ; Ferreira, Teresa ; Grallert, Harald ; Amin, Najaf ; Wu, Guanming ; Willer, Cristen J. ; Raychaudhuri, Soumya ; McCarroll, Steve A. ; Langenberg, Claudia ; Hofmann, Oliver M. ; Dupuis, Josée ; Qi, Lu ; Segrè, Ayellet V. ; van Hoek, Mandy ; Navarro, Pau ; Ardlie, Kristin ; Balkau, Beverley ; Benediktsson, Rafn ; Bennett, Amanda J. ; Blagieva, Roza ; Boerwinkle, Eric ; Bonnycastle, Lori L. ; Bengtsson Boström, Kristina ; Bravenboer, Bert ; Bumpstead, Suzannah ; Burtt, Noël P. ; Charpentier, Guillaume ; Chines, Peter S. ; Cornelis, Marilyn ; Couper, David J. ; Crawford, Gabe ; Doney, Alex S F ; Elliott, Katherine S. ; Elliott, Amanda L. ; Erdos, Michael R. ; Fox, Caroline S. ; Franklin, Christopher S. ; Ganser, Martha ; Gieger, Christian ; Grarup, Niels ; Green, Todd ; Griffin, Simon ; Groves, Christopher J. ; Guiducci, Candace ; Hadjadj, Samy ; Hassanali, Neelam ; Herder, Christian ; Isomaa, Bo ; Jackson, Anne U. ; Johnson, Paul R V ; Jørgensen, Torben ; Kao, Wen H L ; Klopp, Norman ; Kong, Augustine ; Kraft, Peter ; Lauritzen, Torsten ; Li, Man ; Lieverse, Aloysius ; Lindgren, Cecilia M. ; Lyssenko, Valeriya ; Marre, Michel ; Meitinger, Thomas ; Midthjell, Kristian ; Morken, Mario A. ; Narisu, Narisu ; Nilsson, Peter ; Owen, Katharine R. ; Payne, Felicity ; Perry, John R B ; Petersen, Ann Kristin ; Platou, Carl ; Proença, Christine ; Prokopenko, Inga ; Rathmann, Wolfgang ; William Rayner, N. ; Robertson, Neil R. ; Rocheleau, Ghislain ; Roden, Michael ; Sampson, Michael J. ; Saxena, Richa ; Shields, Beverley M. ; Shrader, Peter ; Sigurdsson, Gunnar ; Sparsø, Thomas ; Strassburger, Klaus ; Stringham, Heather M. ; Sun, Qi ; Swift, Amy J. ; Thorand, Barbara ; Tichet, Jean ; Tuomi, Tiinamaija ; van Dam, Rob M. ; van Haeften, Timon W. ; van Herpt, Thijs ; van Vliet-Ostaptchouk, Jana V. ; Bragi Walters, G. ; Weedon, Michael N. ; Wijmenga, Cisca ; Witteman, Jacqueline ; Bergman, Richard N. ; Cauchi, Stephane ; Collins, Francis S. ; Gloyn, Anna L. ; Gyllensten, Ulf ; Hansen, Torben ; Hide, Winston A. ; Hitman, Graham A. ; Hofman, Albert ; Hunter, David J. ; Hveem, Kristian ; Laakso, Markku ; Mohlke, Karen L. ; Morris, Andrew D. ; Palmer, Colin N A ; Pramstaller, Peter P. ; Rudan, Igor ; Sijbrands, Eric ; Stein, Lincoln D. ; Tuomilehto, Jaakko ; Uitterlinden, Andre ; Walker, Mark ; Wareham, Nicholas J. ; Watanabe, Richard M. ; Abecasis, Goncalo R. ; Boehm, Bernhard O. ; Campbell, Harry ; Daly, Mark J. ; Hattersley, Andrew T. ; Hu, Frank B. ; Meigs, James B. ; Pankow, James S. ; Pedersen, Oluf ; Wichmann, H. Erich ; Barroso, Inês ; Florez, Jose C. ; Frayling, Timothy M. ; Groop, Leif ; Sladek, Rob ; Thorsteinsdottir, Unnur ; Wilson, James F. ; Illig, Thomas ; Froguel, Philippe ; van Duijn, Cornelia M. ; Stefansson, Kari ; Altshuler, David ; Boehnke, Michael ; McCarthy, Mark I. ; Blair, Ross D. ; Hill, Andrew A. ; Gerry Hill, B. ; Lewis, David R. ; McNoe, Les A. ; Merriman, Tony R. ; Naik, Dilip K. ; Vicky Phillips, L. ; Thomson, Ian A. ; Topless, Ruth ; Vasudevan, Thodur M. ; Yu, Grace. / Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. In: American Journal of Human Genetics. 2011 ; Vol. 89, No. 5. pp. 619-627.
@article{28a4bd5e3d694f11958b28d50453c6c2,
title = "Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1",
abstract = "Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value <1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p <1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.",
author = "Bown, {Matthew J.} and Jones, {Gregory T.} and Harrison, {Seamus C.} and Wright, {Benjamin J.} and Suzannah Bumpstead and Baas, {Annette F.} and Solveig Gretarsdottir and Badger, {Stephen A.} and Bradley, {Declan T.} and Kevin Burnand and Child, {Anne H.} and Clough, {Rachel E.} and Gillian Cockerill and Hany Hafez and Scott, {D. Julian A} and Simon Futers and Anne Johnson and Soroush Sohrabi and Alberto Smith and Thompson, {Matthew M.} and {van Bockxmeer}, {Frank M.} and Matthew Waltham and Matthiasson, {Stefan E.} and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Blankensteijn, {Jan D.} and Teijink, {Joep A W} and Cisca Wijmenga and {de Graaf}, Jacqueline and Kiemeney, {Lambertus A.} and Assimes, {Themistocles L.} and Ruth McPherson and Lasse Folkersen and Anders Franco-Cereceda and Jutta Palmen and Smith, {Andrew J.} and Nicolas Sylvius and Wild, {John B.} and Mette Refstrup and Sarah Edkins and Rhian Gwilliam and Hunt, {Sarah E.} and Simon Potter and Lindholt, {Jes S.} and Ruth Frikke-Schmidt and Anne Tybj{\ae}rg-Hansen and Hughes, {Anne E.} and Jonathan Golledge and Norman, {Paul E.} and {van Rij}, Andre and Powell, {Janet T.} and Per Eriksson and Kari Stefansson and Thompson, {John R.} and Humphries, {Steve E.} and Sayers, {Robert D.} and Panos Deloukas and Samani, {Nilesh J.} and Heribert Schunkert and K{\"o}nig, {Inke R.} and Sekar Kathiresan and Reilly, {Muredach P.} and Assimes, {Themistocles L.} and Hilma Holm and Michael Preuss and Stewart, {Alexandre F R} and Maja Barbalic and Christian Gieger and Devin Absher and Zouhair Aherrahrou and Hooman Allayee and David Altshuler and Anand, {Sonia S.} and Karl Andersen and Anderson, {Jeffrey L.} and Diego Ardissino and Ball, {Stephen G.} and Balmforth, {Anthony J.} and Barnes, {Timothy A.} and Becker, {Diane M.} and Becker, {Lewis C.} and Klaus Berger and Bis, {Joshua C.} and {Matthijs Boekholdt}, S. and Eric Boerwinkle and Braund, {Peter S.} and Brown, {Morris J.} and {Susan Burnett}, Mary and Ian Buysschaert and Carlquist, {John F.} and Li Chen and Sven Cichon and Veryan Codd and Davies, {Robert W.} and George Dedoussis and Abbas Dehghan and Serkalem Demissie and Devaney, {Joseph M.} and Patrick Diemert and Ron Do and Angela Doering and Sandra Eifert and {El Mokhtari}, {Nour Eddine} and Ellis, {Stephen G.} and Roberto Elosua and Engert, {James C.} and Epstein, {Stephen E.} and {de Faire}, Ulf and Marcus Fischer and Folsom, {Aaron R.} and Jennifer Freyer and Bruna Gigante and Domenico Girelli and Solveig Gretarsdottir and Vilmundur Gudnason and Gulcher, {Jeffrey R.} and Eran Halperin and Naomi Hammond and Hazen, {Stanley L.} and Albert Hofman and Horne, {Benjamin D.} and Thomas Illig and Carlos Iribarren and Jones, {Gregory T.} and {Wouter Jukema}, J. and Kaiser, {Michael A.} and Kaplan, {Lee M.} and Kastelein, {John J P} and Khaw, {Kay Tee} and Knowles, {Joshua W.} and Genovefa Kolovou and Augustine Kong and Reijo Laaksonen and Diether Lambrechts and Karin Leander and Guillaume Lettre and Mingyao Li and Wolfgang Lieb and Christina Loley and Lotery, {Andrew J.} and Mannucci, {Pier M.} and Seraya Maouche and Nicola Martinelli and McKeown, {Pascal P.} and Christa Meisinger and Thomas Meitinger and Olle Melander and {Angelica Merlini}, Pier and Vincent Mooser and Thomas Morgan and M{\"u}hleisen, {Thomas W.} and Muhlestein, {Joseph B.} and Thomas M{\"u}nzel and Kiran Musunuru and Janja Nahrstaedt and Nelson, {Christopher P.} and N{\"o}then, {Markus M.} and Oliviero Olivieri and Patel, {Riyaz S.} and Patterson, {Chris C.} and Annette Peters and Flora Peyvandi and Liming Qu and Quyyumi, {Arshed A.} and Rader, {Daniel J.} and Rallidis, {Loukianos S.} and Catherine Rice and Rosendaal, {Frits R.} and Diana Rubin and Veikko Salomaa and {Lourdes Sampietro}, M. and Sandhu, {Manj S.} and Eric Schadt and Arne Sch{\"a}fer and Arne Schillert and Stefan Schreiber and J{\"u}rgen Schrezenmeir and Schwartz, {Stephen M.} and Siscovick, {David S.} and Mohan Sivananthan and Suthesh Sivapalaratnam and Albert Smith and Smith, {Tamara B.} and Snoep, {Jaapjan D.} and Nicole Soranzo and Spertus, {John A.} and Klaus Stark and Kathy Stirrups and Monika Stoll and {Wilson Tang}, {W. H.} and Stephanie Tennstedt and Gudmundur Thorgeirsson and Gudmar Thorleifsson and Maciej Tomaszewski and Uitterlinden, {Andre G.} and {van Rij}, {Andre M.} and Voight, {Benjamin F.} and Wareham, {Nick J.} and Wells, {George A.} and Wichmann, {H. Erich} and Wild, {Philipp S.} and Christina Willenborg and Witteman, {Jaqueline C M} and Wright, {Benjamin J.} and Shu Ye and Tanja Zeller and Andreas Ziegler and Francois Cambien and Goodall, {Alison H.} and {Adrienne Cupples}, L. and Thomas Quertermous and Winfried M{\"a}rz and Christian Hengstenberg and Stefan Blankenberg and Ouwehand, {Willem H.} and Hall, {Alistair S.} and Panos Deloukas and Thompson, {John R.} and Kari Stefansson and Robert Roberts and Unnur Thorsteinsdottir and O'Donnell, {Christopher J.} and Ruth McPherson and Jeanette Erdmann and Samani, {Nilesh J.} and Christopher Newton-Cheh and Toby Johnson and Vesela Gateva and Tobin, {Martin D.} and Murielle Bochud and Lachlan Coin and Najjar, {Samer S.} and {Hua Zhao}, Jing and Heath, {Simon C.} and Susana Eyheramendy and Konstantinos Papadakis and Voight, {Benjamin F.} and Scott, {Laura J.} and Feng Zhang and Martin Farrall and Toshiko Tanaka and Chris Wallace and Chambers, {John C.} and Khaw, {Kay Tee} and Peter Nilsson and {van der Harst}, Pim and Silvia Polidoro and Grobbee, {Diederick E.} and Onland-Moret, {N. Charlotte} and Bots, {Michiel L.} and Wain, {Louise V.} and Elliott, {Katherine S.} and Alexander Teumer and Jian'an Luan and Gavin Lucas and Johanna Kuusisto and Burton, {Paul R.} and David Hadley and McArdle, {Wendy L.} and Morris Brown and Anna Dominiczak and Newhouse, {Stephen J.} and Samani, {Nilesh J.} and John Webster and Eleftheria Zeggini and Beckmann, {Jacques S.} and Sven Bergmann and Noha Lim and Kijoung Song and Peter Vollenweider and Gerard Waeber and Waterworth, {Dawn M.} and Xin Yuan and Leif Groop and Marju Orho-Melander and Alessandra Allione and {Di Gregorio}, Alessandra and Simonetta Guarrera and Salvatore Panico and Fulvio Ricceri and Valeria Romanazzi and Carlotta Sacerdote and Paolo Vineis and In{\^e}s Barroso and Sandhu, {Manjinder S.} and Luben, {Robert N.} and Crawford, {Gabriel J.} and Pekka Jousilahti and Markus Perola and Michael Boehnke and Bonnycastle, {Lori L.} and Collins, {Francis S.} and Jackson, {Anne U.} and Mohlke, {Karen L.} and Stringham, {Heather M.} and Valle, {Timo T.} and Willer, {Cristen J.} and Bergman, {Richard N.} and Morken, {Mario A.} and Angela D{\"o}ring and Christian Gieger and Thomas Illig and Thomas Meitinger and Elin Org and Arne Pfeufer and Wichmann, {H. Erich} and Sekar Kathiresan and Jaume Marrugat and O'Donnell, {Christopher J.} and Schwartz, {Stephen M.} and Siscovick, {David S.} and Isaac Subirana and Freimer, {Nelson B.} and Hartikainen, {Anna Liisa} and McCarthy, {Mark I.} and O'Reilly, {Paul F.} and Leena Peltonen and Anneli Pouta and {de Jong}, {Paul E.} and Harold Snieder and {van Gilst}, {Wiek H.} and Robert Clarke and Anuj Goel and Anders Hamsten and Peden, {John F.} and Udo Seedorf and Syv{\"a}nen, {Ann Christine} and Giovanni Tognoni and Lakatta, {Edward G.} and Serena Sanna and Paul Scheet and David Schlessinger and Angelo Scuteri and Marcus D{\"o}rr and Florian Ernst and Felix, {Stephan B.} and Georg Homuth and Roberto Lorbeer and Thorsten Reffelmann and Rainer Rettig and Uwe V{\"o}lker and Pilar Galan and Gut, {Ivo G.} and Serge Hercberg and {Mark Lathrop}, G. and Diana Zelenika and Panos Deloukas and Nicole Soranzo and Williams, {Frances M.} and Guangju Zhai and Veikko Salomaa and Markku Laakso and Roberto Elosua and Forouhi, {Nita G.} and Henry V{\"o}lzke and Uiterwaal, {Cuno S.} and {van der Schouw}, {Yvonne T.} and Numans, {Mattijs E.} and Giuseppe Matullo and Gerjan Navis and G{\"o}ran Berglund and Bingham, {Sheila A.} and Kooner, {Jaspal S.} and Connell, {John M.} and Stefania Bandinelli and Luigi Ferrucci and Hugh Watkins and Spector, {Tim D.} and Jaakko Tuomilehto and David Altshuler and Strachan, {David P.} and Maris Laan and Pierre Meneton and Wareham, {Nicholas J.} and Manuela Uda and Jarvelin, {Marjo Riitta} and Vincent Mooser and Olle Melander and Loos, {Ruth J F} and Paul Elliott and Abecasis, {Gon{\cc}alo R.} and Mark Caulfield and Munroe, {Patricia B.} and Voight, {Benjamin F.} and Scott, {Laura J.} and Valgerdur Steinthorsdottir and Morris, {Andrew P.} and Christian Dina and Welch, {Ryan P.} and Eleftheria Zeggini and Cornelia Huth and Aulchenko, {Yurii S.} and Gudmar Thorleifsson and McCulloch, {Laura J.} and Teresa Ferreira and Harald Grallert and Najaf Amin and Guanming Wu and Willer, {Cristen J.} and Soumya Raychaudhuri and McCarroll, {Steve A.} and Claudia Langenberg and Hofmann, {Oliver M.} and Jos{\'e}e Dupuis and Lu Qi and Segr{\`e}, {Ayellet V.} and {van Hoek}, Mandy and Pau Navarro and Kristin Ardlie and Beverley Balkau and Rafn Benediktsson and Bennett, {Amanda J.} and Roza Blagieva and Eric Boerwinkle and Bonnycastle, {Lori L.} and {Bengtsson Bostr{\"o}m}, Kristina and Bert Bravenboer and Suzannah Bumpstead and Burtt, {No{\"e}l P.} and Guillaume Charpentier and Chines, {Peter S.} and Marilyn Cornelis and Couper, {David J.} and Gabe Crawford and Doney, {Alex S F} and Elliott, {Katherine S.} and Elliott, {Amanda L.} and Erdos, {Michael R.} and Fox, {Caroline S.} and Franklin, {Christopher S.} and Martha Ganser and Christian Gieger and Niels Grarup and Todd Green and Simon Griffin and Groves, {Christopher J.} and Candace Guiducci and Samy Hadjadj and Neelam Hassanali and Christian Herder and Bo Isomaa and Jackson, {Anne U.} and Johnson, {Paul R V} and Torben J{\o}rgensen and Kao, {Wen H L} and Norman Klopp and Augustine Kong and Peter Kraft and Torsten Lauritzen and Man Li and Aloysius Lieverse and Lindgren, {Cecilia M.} and Valeriya Lyssenko and Michel Marre and Thomas Meitinger and Kristian Midthjell and Morken, {Mario A.} and Narisu Narisu and Peter Nilsson and Owen, {Katharine R.} and Felicity Payne and Perry, {John R B} and Petersen, {Ann Kristin} and Carl Platou and Christine Proen{\cc}a and Inga Prokopenko and Wolfgang Rathmann and {William Rayner}, N. and Robertson, {Neil R.} and Ghislain Rocheleau and Michael Roden and Sampson, {Michael J.} and Richa Saxena and Shields, {Beverley M.} and Peter Shrader and Gunnar Sigurdsson and Thomas Spars{\o} and Klaus Strassburger and Stringham, {Heather M.} and Qi Sun and Swift, {Amy J.} and Barbara Thorand and Jean Tichet and Tiinamaija Tuomi and {van Dam}, {Rob M.} and {van Haeften}, {Timon W.} and {van Herpt}, Thijs and {van Vliet-Ostaptchouk}, {Jana V.} and {Bragi Walters}, G. and Weedon, {Michael N.} and Cisca Wijmenga and Jacqueline Witteman and Bergman, {Richard N.} and Stephane Cauchi and Collins, {Francis S.} and Gloyn, {Anna L.} and Ulf Gyllensten and Torben Hansen and Hide, {Winston A.} and Hitman, {Graham A.} and Albert Hofman and Hunter, {David J.} and Kristian Hveem and Markku Laakso and Mohlke, {Karen L.} and Morris, {Andrew D.} and Palmer, {Colin N A} and Pramstaller, {Peter P.} and Igor Rudan and Eric Sijbrands and Stein, {Lincoln D.} and Jaakko Tuomilehto and Andre Uitterlinden and Mark Walker and Wareham, {Nicholas J.} and Watanabe, {Richard M.} and Abecasis, {Goncalo R.} and Boehm, {Bernhard O.} and Harry Campbell and Daly, {Mark J.} and Hattersley, {Andrew T.} and Hu, {Frank B.} and Meigs, {James B.} and Pankow, {James S.} and Oluf Pedersen and Wichmann, {H. Erich} and In{\^e}s Barroso and Florez, {Jose C.} and Frayling, {Timothy M.} and Leif Groop and Rob Sladek and Unnur Thorsteinsdottir and Wilson, {James F.} and Thomas Illig and Philippe Froguel and {van Duijn}, {Cornelia M.} and Kari Stefansson and David Altshuler and Michael Boehnke and McCarthy, {Mark I.} and Blair, {Ross D.} and Hill, {Andrew A.} and {Gerry Hill}, B. and Lewis, {David R.} and McNoe, {Les A.} and Merriman, {Tony R.} and Naik, {Dilip K.} and {Vicky Phillips}, L. and Thomson, {Ian A.} and Ruth Topless and Vasudevan, {Thodur M.} and Grace Yu",
year = "2011",
month = "11",
day = "11",
doi = "10.1016/j.ajhg.2011.10.002",
language = "English",
volume = "89",
pages = "619--627",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

AU - Bown, Matthew J.

AU - Jones, Gregory T.

AU - Harrison, Seamus C.

AU - Wright, Benjamin J.

AU - Bumpstead, Suzannah

AU - Baas, Annette F.

AU - Gretarsdottir, Solveig

AU - Badger, Stephen A.

AU - Bradley, Declan T.

AU - Burnand, Kevin

AU - Child, Anne H.

AU - Clough, Rachel E.

AU - Cockerill, Gillian

AU - Hafez, Hany

AU - Scott, D. Julian A

AU - Futers, Simon

AU - Johnson, Anne

AU - Sohrabi, Soroush

AU - Smith, Alberto

AU - Thompson, Matthew M.

AU - van Bockxmeer, Frank M.

AU - Waltham, Matthew

AU - Matthiasson, Stefan E.

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Blankensteijn, Jan D.

AU - Teijink, Joep A W

AU - Wijmenga, Cisca

AU - de Graaf, Jacqueline

AU - Kiemeney, Lambertus A.

AU - Assimes, Themistocles L.

AU - McPherson, Ruth

AU - Folkersen, Lasse

AU - Franco-Cereceda, Anders

AU - Palmen, Jutta

AU - Smith, Andrew J.

AU - Sylvius, Nicolas

AU - Wild, John B.

AU - Refstrup, Mette

AU - Edkins, Sarah

AU - Gwilliam, Rhian

AU - Hunt, Sarah E.

AU - Potter, Simon

AU - Lindholt, Jes S.

AU - Frikke-Schmidt, Ruth

AU - Tybjærg-Hansen, Anne

AU - Hughes, Anne E.

AU - Golledge, Jonathan

AU - Norman, Paul E.

AU - van Rij, Andre

AU - Powell, Janet T.

AU - Eriksson, Per

AU - Stefansson, Kari

AU - Thompson, John R.

AU - Humphries, Steve E.

AU - Sayers, Robert D.

AU - Deloukas, Panos

AU - Samani, Nilesh J.

AU - Schunkert, Heribert

AU - König, Inke R.

AU - Kathiresan, Sekar

AU - Reilly, Muredach P.

AU - Assimes, Themistocles L.

AU - Holm, Hilma

AU - Preuss, Michael

AU - Stewart, Alexandre F R

AU - Barbalic, Maja

AU - Gieger, Christian

AU - Absher, Devin

AU - Aherrahrou, Zouhair

AU - Allayee, Hooman

AU - Altshuler, David

AU - Anand, Sonia S.

AU - Andersen, Karl

AU - Anderson, Jeffrey L.

AU - Ardissino, Diego

AU - Ball, Stephen G.

AU - Balmforth, Anthony J.

AU - Barnes, Timothy A.

AU - Becker, Diane M.

AU - Becker, Lewis C.

AU - Berger, Klaus

AU - Bis, Joshua C.

AU - Matthijs Boekholdt, S.

AU - Boerwinkle, Eric

AU - Braund, Peter S.

AU - Brown, Morris J.

AU - Susan Burnett, Mary

AU - Buysschaert, Ian

AU - Carlquist, John F.

AU - Chen, Li

AU - Cichon, Sven

AU - Codd, Veryan

AU - Davies, Robert W.

AU - Dedoussis, George

AU - Dehghan, Abbas

AU - Demissie, Serkalem

AU - Devaney, Joseph M.

AU - Diemert, Patrick

AU - Do, Ron

AU - Doering, Angela

AU - Eifert, Sandra

AU - El Mokhtari, Nour Eddine

AU - Ellis, Stephen G.

AU - Elosua, Roberto

AU - Engert, James C.

AU - Epstein, Stephen E.

AU - de Faire, Ulf

AU - Fischer, Marcus

AU - Folsom, Aaron R.

AU - Freyer, Jennifer

AU - Gigante, Bruna

AU - Girelli, Domenico

AU - Gretarsdottir, Solveig

AU - Gudnason, Vilmundur

AU - Gulcher, Jeffrey R.

AU - Halperin, Eran

AU - Hammond, Naomi

AU - Hazen, Stanley L.

AU - Hofman, Albert

AU - Horne, Benjamin D.

AU - Illig, Thomas

AU - Iribarren, Carlos

AU - Jones, Gregory T.

AU - Wouter Jukema, J.

AU - Kaiser, Michael A.

AU - Kaplan, Lee M.

AU - Kastelein, John J P

AU - Khaw, Kay Tee

AU - Knowles, Joshua W.

AU - Kolovou, Genovefa

AU - Kong, Augustine

AU - Laaksonen, Reijo

AU - Lambrechts, Diether

AU - Leander, Karin

AU - Lettre, Guillaume

AU - Li, Mingyao

AU - Lieb, Wolfgang

AU - Loley, Christina

AU - Lotery, Andrew J.

AU - Mannucci, Pier M.

AU - Maouche, Seraya

AU - Martinelli, Nicola

AU - McKeown, Pascal P.

AU - Meisinger, Christa

AU - Meitinger, Thomas

AU - Melander, Olle

AU - Angelica Merlini, Pier

AU - Mooser, Vincent

AU - Morgan, Thomas

AU - Mühleisen, Thomas W.

AU - Muhlestein, Joseph B.

AU - Münzel, Thomas

AU - Musunuru, Kiran

AU - Nahrstaedt, Janja

AU - Nelson, Christopher P.

AU - Nöthen, Markus M.

AU - Olivieri, Oliviero

AU - Patel, Riyaz S.

AU - Patterson, Chris C.

AU - Peters, Annette

AU - Peyvandi, Flora

AU - Qu, Liming

AU - Quyyumi, Arshed A.

AU - Rader, Daniel J.

AU - Rallidis, Loukianos S.

AU - Rice, Catherine

AU - Rosendaal, Frits R.

AU - Rubin, Diana

AU - Salomaa, Veikko

AU - Lourdes Sampietro, M.

AU - Sandhu, Manj S.

AU - Schadt, Eric

AU - Schäfer, Arne

AU - Schillert, Arne

AU - Schreiber, Stefan

AU - Schrezenmeir, Jürgen

AU - Schwartz, Stephen M.

AU - Siscovick, David S.

AU - Sivananthan, Mohan

AU - Sivapalaratnam, Suthesh

AU - Smith, Albert

AU - Smith, Tamara B.

AU - Snoep, Jaapjan D.

AU - Soranzo, Nicole

AU - Spertus, John A.

AU - Stark, Klaus

AU - Stirrups, Kathy

AU - Stoll, Monika

AU - Wilson Tang, W. H.

AU - Tennstedt, Stephanie

AU - Thorgeirsson, Gudmundur

AU - Thorleifsson, Gudmar

AU - Tomaszewski, Maciej

AU - Uitterlinden, Andre G.

AU - van Rij, Andre M.

AU - Voight, Benjamin F.

AU - Wareham, Nick J.

AU - Wells, George A.

AU - Wichmann, H. Erich

AU - Wild, Philipp S.

AU - Willenborg, Christina

AU - Witteman, Jaqueline C M

AU - Wright, Benjamin J.

AU - Ye, Shu

AU - Zeller, Tanja

AU - Ziegler, Andreas

AU - Cambien, Francois

AU - Goodall, Alison H.

AU - Adrienne Cupples, L.

AU - Quertermous, Thomas

AU - März, Winfried

AU - Hengstenberg, Christian

AU - Blankenberg, Stefan

AU - Ouwehand, Willem H.

AU - Hall, Alistair S.

AU - Deloukas, Panos

AU - Thompson, John R.

AU - Stefansson, Kari

AU - Roberts, Robert

AU - Thorsteinsdottir, Unnur

AU - O'Donnell, Christopher J.

AU - McPherson, Ruth

AU - Erdmann, Jeanette

AU - Samani, Nilesh J.

AU - Newton-Cheh, Christopher

AU - Johnson, Toby

AU - Gateva, Vesela

AU - Tobin, Martin D.

AU - Bochud, Murielle

AU - Coin, Lachlan

AU - Najjar, Samer S.

AU - Hua Zhao, Jing

AU - Heath, Simon C.

AU - Eyheramendy, Susana

AU - Papadakis, Konstantinos

AU - Voight, Benjamin F.

AU - Scott, Laura J.

AU - Zhang, Feng

AU - Farrall, Martin

AU - Tanaka, Toshiko

AU - Wallace, Chris

AU - Chambers, John C.

AU - Khaw, Kay Tee

AU - Nilsson, Peter

AU - van der Harst, Pim

AU - Polidoro, Silvia

AU - Grobbee, Diederick E.

AU - Onland-Moret, N. Charlotte

AU - Bots, Michiel L.

AU - Wain, Louise V.

AU - Elliott, Katherine S.

AU - Teumer, Alexander

AU - Luan, Jian'an

AU - Lucas, Gavin

AU - Kuusisto, Johanna

AU - Burton, Paul R.

AU - Hadley, David

AU - McArdle, Wendy L.

AU - Brown, Morris

AU - Dominiczak, Anna

AU - Newhouse, Stephen J.

AU - Samani, Nilesh J.

AU - Webster, John

AU - Zeggini, Eleftheria

AU - Beckmann, Jacques S.

AU - Bergmann, Sven

AU - Lim, Noha

AU - Song, Kijoung

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Waterworth, Dawn M.

AU - Yuan, Xin

AU - Groop, Leif

AU - Orho-Melander, Marju

AU - Allione, Alessandra

AU - Di Gregorio, Alessandra

AU - Guarrera, Simonetta

AU - Panico, Salvatore

AU - Ricceri, Fulvio

AU - Romanazzi, Valeria

AU - Sacerdote, Carlotta

AU - Vineis, Paolo

AU - Barroso, Inês

AU - Sandhu, Manjinder S.

AU - Luben, Robert N.

AU - Crawford, Gabriel J.

AU - Jousilahti, Pekka

AU - Perola, Markus

AU - Boehnke, Michael

AU - Bonnycastle, Lori L.

AU - Collins, Francis S.

AU - Jackson, Anne U.

AU - Mohlke, Karen L.

AU - Stringham, Heather M.

AU - Valle, Timo T.

AU - Willer, Cristen J.

AU - Bergman, Richard N.

AU - Morken, Mario A.

AU - Döring, Angela

AU - Gieger, Christian

AU - Illig, Thomas

AU - Meitinger, Thomas

AU - Org, Elin

AU - Pfeufer, Arne

AU - Wichmann, H. Erich

AU - Kathiresan, Sekar

AU - Marrugat, Jaume

AU - O'Donnell, Christopher J.

AU - Schwartz, Stephen M.

AU - Siscovick, David S.

AU - Subirana, Isaac

AU - Freimer, Nelson B.

AU - Hartikainen, Anna Liisa

AU - McCarthy, Mark I.

AU - O'Reilly, Paul F.

AU - Peltonen, Leena

AU - Pouta, Anneli

AU - de Jong, Paul E.

AU - Snieder, Harold

AU - van Gilst, Wiek H.

AU - Clarke, Robert

AU - Goel, Anuj

AU - Hamsten, Anders

AU - Peden, John F.

AU - Seedorf, Udo

AU - Syvänen, Ann Christine

AU - Tognoni, Giovanni

AU - Lakatta, Edward G.

AU - Sanna, Serena

AU - Scheet, Paul

AU - Schlessinger, David

AU - Scuteri, Angelo

AU - Dörr, Marcus

AU - Ernst, Florian

AU - Felix, Stephan B.

AU - Homuth, Georg

AU - Lorbeer, Roberto

AU - Reffelmann, Thorsten

AU - Rettig, Rainer

AU - Völker, Uwe

AU - Galan, Pilar

AU - Gut, Ivo G.

AU - Hercberg, Serge

AU - Mark Lathrop, G.

AU - Zelenika, Diana

AU - Deloukas, Panos

AU - Soranzo, Nicole

AU - Williams, Frances M.

AU - Zhai, Guangju

AU - Salomaa, Veikko

AU - Laakso, Markku

AU - Elosua, Roberto

AU - Forouhi, Nita G.

AU - Völzke, Henry

AU - Uiterwaal, Cuno S.

AU - van der Schouw, Yvonne T.

AU - Numans, Mattijs E.

AU - Matullo, Giuseppe

AU - Navis, Gerjan

AU - Berglund, Göran

AU - Bingham, Sheila A.

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AU - Yu, Grace

PY - 2011/11/11

Y1 - 2011/11/11

N2 - Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value <1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p <1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

AB - Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value <1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p <1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

UR - http://www.scopus.com/inward/record.url?scp=84945173643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945173643&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2011.10.002

DO - 10.1016/j.ajhg.2011.10.002

M3 - Article

AN - SCOPUS:84945173643

VL - 89

SP - 619

EP - 627

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -