Directional dominance on stature and cognition in diverse human populations

Peter K. Joshi, Tonu Esko, Hannele Mattsson, Niina Eklund, Ilaria Gandin, Teresa Nutile, Anne U. Jackson, Claudia Schurmann, Albert V. Smith, Weihua Zhang, Yukinori Okada, Alena Stančáková, Jessica D. Faul, Wei Zhao, Traci M. Bartz, Maria Pina Concas, Nora Franceschini, Stefan Enroth, Veronique Vitart, Stella Trompet & 339 others Xiuqing Guo, Daniel I. Chasman, Jeffrey R. O'Connel, Tanguy Corre, Suraj S. Nongmaithem, Yuning Chen, Massimo Mangino, Daniela Ruggiero, Michela Traglia, Aliki Eleni Farmaki, Tim Kacprowski, Andrew Bjonnes, Ashley Van Der Spek, Ying Wu, Anil K. Giri, Lisa R. Yanek, Lihua Wang, Edith Hofer, Cornelius A. Rietveld, Olga McLeod, Marilyn C. Cornelis, Cristian Pattaro, Niek Verweij, Clemens Baumbach, Abdel Abdellaoui, Helen R. Warren, Dragana Vuckovic, Hao Mei, Claude Bouchard, John R B Perry, Stefania Cappellani, Saira S. Mirza, Miles C. Benton, Ulrich Broeckel, Sarah E. Medland, Penelope A. Lind, Giovanni Malerba, Alexander Drong, Loic Yengo, Lawrence F. Bielak, Degui Zhi, Peter J. Van Der Most, Daniel Shriner, Reedik Mägi, Gibran Hemani, Tugce Karaderi, Zhaoming Wang, Tian Liu, Ilja Demuth, Jing Hua Zhao, Weihua Meng, Lazaros Lataniotis, Sander W. Van Der Laan, Jonathan P. Bradfield, Andrew R. Wood, Amelie Bonnefond, Tarunveer S. Ahluwalia, Leanne M. Hall, Erika Salvi, Seyhan Yazar, Lisbeth Carstensen, Hugoline G. De Haan, Mark Abney, Uzma Afzal, Matthew A. Allison, Najaf Amin, Folkert W. Asselbergs, Stephan J L Bakker, R. Graham Barr, Sebastian E. Baumeister, Daniel J. Benjamin, Sven Bergmann, Eric Boerwinkle, Erwin P. Bottinger, Archie Campbell, Aravinda Chakravarti, Yingleong Chan, Stephen J. Chanock, Constance Chen, Y. D Ida Chen, Francis S. Collins, John Connell, Adolfo Correa, L. Adrienne Cupples, George Davey Smith, Gail Davies, Marcus Dörr, Georg Ehret, Stephen B. Ellis, Bjarke Feenstra, Mary F. Feitosa, Ian Ford, Caroline S. Fox, Timothy M. Frayling, Nele Friedrich, Frank Geller, Generation Scotland, Irina Gillham-Nasenya, Omri Gottesman, Misa Graff, Francine Grodstein, Charles Gu, Chris Haley, Christopher J. Hammond, Sarah E. Harris, Tamara B. Harris, Nicholas D. Hastie, Nancy L. Heard-Costa, Kauko Heikkilä, Lynne J. Hocking, Georg Homuth, Jouke Jan Hottenga, Jinyan Huang, Jennifer E. Huffman, Pirro G. Hysi, M. Arfan Ikram, Erik Ingelsson, Anni Joensuu, Åsa Johansson, Pekka Jousilahti, J. Wouter Jukema, Mika Kähönen, Yoichiro Kamatani, Stavroula Kanoni, Shona M. Kerr, Nazir M. Khan, Philipp Koellinger, Heikki A. Koistinen, Manraj K. Kooner, Michiaki Kubo, Johanna Kuusisto, Jari Lahti, Lenore J. Launer, Rodney A. Lea, Benjamin Lehne, Terho Lehtimäki, David C M Liewald, Lars Lind, Marie Loh, Marja Liisa Lokki, Stephanie J. London, Stephanie J. Loomis, Anu Loukola, Yingchang Lu, Thomas Lumley, Annamari Lundqvist, Satu Männistö, Pedro Marques-Vidal, Corrado Masciullo, Angela Matchan, Rasika A. Mathias, Koichi Matsuda, James B. Meigs, Christa Meisinger, Thomas Meitinger, Cristina Menni, Frank D. Mentch, Evelin Mihailov, Lili Milani, May E. Montasser, Grant W. Montgomery, Alanna Morrison, Richard H. Myers, Rajiv Nadukuru, Pau Navarro, Mari Nalis, Markku S. Nieminen, Ilja M. Nolte, George T. O'Connor, Adesola Ogunniyi, Sandosh Padmanabhan, Walter R. Palmas, James S. Pankow, Inga Patarcic, Francesca Pavani, Patricia A. Peyser, Kirsi Pietilainen, Neil Poulter, Inga Prokopenko, Sarju Ralhan, Paul Redmond, Stephen S. Rich, Harri Rissanen, Antonietta Robino, Lynda M. Rose, Richard Rose, Cinzia Sala, Babatunde Salako, Veikko Salomaa, Antti Pekka Sarin, Richa Saxena, Helena Schmidt, Laura J. Scott, William R. Scott, Bengt Sennblad, Sudha Seshadri, Peter Sever, Smeeta Shrestha, Blair H. Smith, Jennifer A. Smith, Nicole Soranzo, Nona Sotoodehnia, Lorraine Southam, Alice V. Stanton, Maria G. Stathopoulou, Konstantin Strauch, Rona J. Strawbridge, Matthew J. Suderman, Nikhil Tandon, Sian Tsun Tang, Kent D. Taylor, Bamidele O. Tayo, Anna Maria Töglhofer, Maciej Tomaszewski, Natalia Tšernikova, Jaakko Tuomilehto, Andre G. Uitterlinden, Dhananjay Vaidya, Astrid Van Hylckama Vlieg, Jessica Van Setten, Tuula Vasankari, Sailaja Vedantam, Efthymia Vlachopoulou, Diego Vozzi, Eero Vuoksimaa, Melanie Waldenberger, Erin B. Ware, William Wentworth-Shields, John B. Whitfield, Sarah Wild, Gonneke Willemsen, Chittaranjan S. Yajnik, Jie Yao, Gianluigi Zaza, Xiaofeng Zhu, Rany M. Salem, Mads Melbye, Hans Bisgaard, Nilesh J. Samani, Daniele Cusi, David A. Mackey, Richard S. Cooper, Philippe Froguel, Gerard Pasterkamp, Struan F A Grant, Hakon Hakonarson, Luigi Ferrucci, Robert A. Scott, Andrew D. Morris, Colin N A Palmer, George Dedoussis, Panos Deloukas, Lars Bertram, Ulman Lindenberger, Sonja I. Berndt, Cecilia M. Lindgren, Nicholas J. Timpson, Anke Tönjes, Patricia B. Munroe, Thorkild I A Sørensen, Charles N. Rotimi, Donna K. Arnett, Albertine J. Oldehinkel, Sharon L R Kardia, Beverley Balkau, Giovanni Gambaro, Andrew P. Morris, Johan G. Eriksson, Margie J. Wright, Nicholas G. Martin, Steven C. Hunt, John M. Starr, Ian J. Deary, Lyn R. Griffiths, Henning Tiemeier, Nicola Pirastu, Jaakko Kaprio, Nicholas J. Wareham, Louis Pérusse, James G. Wilson, Giorgia Girotto, Mark J. Caulfield, Olli Raitakari, Dorret I. Boomsma, Christian Gieger, Pim Van Der Harst, Andrew A. Hicks, Peter Kraft, Juha Sinisalo, Paul Knekt, Magnus Johannesson, Patrik K E Magnusson, Anders Hamsten, Reinhold Schmidt, Ingrid B. Borecki, Erkki Vartiainen, Diane M. Becker, Dwaipayan Bharadwaj, Karen L. Mohlke, Michael Boehnke, Cornelia M. Van Duijn, Dharambir K. Sanghera, Alexander Teumer, Eleftheria Zeggini, Andres Metspalu, Paolo Gasparini, Sheila Ulivi, Carole Ober, Daniela Toniolo, Igor Rudan, David J. Porteous, Marina Ciullo, Tim D. Spector, Caroline Hayward, Josée Dupuis, Ruth J F Loos, Alan F. Wright, Giriraj R. Chandak, Peter Vollenweider, Alan R. Shuldiner, Paul M. Ridker, Jerome I. Rotter, Naveed Sattar, Ulf Gyllensten, Kari E. North, Mario Pirastu, Bruce M. Psaty, David R. Weir, Markku Laakso, Vilmundur Gudnason, Atsushi Takahashi, John C. Chambers, Jaspal S. Kooner, David P. Strachan, Harry Campbell, Joel N. Hirschhorn, Markus Perola, Ozren Polašek, James F. Wilson

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P <1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Original languageEnglish
Pages (from-to)459-462
Number of pages4
JournalNature
Volume523
Issue number7561
DOIs
Publication statusPublished - Jul 23 2015

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Cognition
Genome
Population
Aptitude
Inbreeding
Forced Expiratory Volume
LDL Cholesterol
Public Health
Blood Pressure
Education
Lung
Health
Late Onset Disorders
Power (Psychology)

ASJC Scopus subject areas

  • General

Cite this

Joshi, P. K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., ... Wilson, J. F. (2015). Directional dominance on stature and cognition in diverse human populations. Nature, 523(7561), 459-462. https://doi.org/10.1038/nature14618

Directional dominance on stature and cognition in diverse human populations. / Joshi, Peter K.; Esko, Tonu; Mattsson, Hannele; Eklund, Niina; Gandin, Ilaria; Nutile, Teresa; Jackson, Anne U.; Schurmann, Claudia; Smith, Albert V.; Zhang, Weihua; Okada, Yukinori; Stančáková, Alena; Faul, Jessica D.; Zhao, Wei; Bartz, Traci M.; Concas, Maria Pina; Franceschini, Nora; Enroth, Stefan; Vitart, Veronique; Trompet, Stella; Guo, Xiuqing; Chasman, Daniel I.; O'Connel, Jeffrey R.; Corre, Tanguy; Nongmaithem, Suraj S.; Chen, Yuning; Mangino, Massimo; Ruggiero, Daniela; Traglia, Michela; Farmaki, Aliki Eleni; Kacprowski, Tim; Bjonnes, Andrew; Van Der Spek, Ashley; Wu, Ying; Giri, Anil K.; Yanek, Lisa R.; Wang, Lihua; Hofer, Edith; Rietveld, Cornelius A.; McLeod, Olga; Cornelis, Marilyn C.; Pattaro, Cristian; Verweij, Niek; Baumbach, Clemens; Abdellaoui, Abdel; Warren, Helen R.; Vuckovic, Dragana; Mei, Hao; Bouchard, Claude; Perry, John R B; Cappellani, Stefania; Mirza, Saira S.; Benton, Miles C.; Broeckel, Ulrich; Medland, Sarah E.; Lind, Penelope A.; Malerba, Giovanni; Drong, Alexander; Yengo, Loic; Bielak, Lawrence F.; Zhi, Degui; Van Der Most, Peter J.; Shriner, Daniel; Mägi, Reedik; Hemani, Gibran; Karaderi, Tugce; Wang, Zhaoming; Liu, Tian; Demuth, Ilja; Zhao, Jing Hua; Meng, Weihua; Lataniotis, Lazaros; Van Der Laan, Sander W.; Bradfield, Jonathan P.; Wood, Andrew R.; Bonnefond, Amelie; Ahluwalia, Tarunveer S.; Hall, Leanne M.; Salvi, Erika; Yazar, Seyhan; Carstensen, Lisbeth; De Haan, Hugoline G.; Abney, Mark; Afzal, Uzma; Allison, Matthew A.; Amin, Najaf; Asselbergs, Folkert W.; Bakker, Stephan J L; Barr, R. Graham; Baumeister, Sebastian E.; Benjamin, Daniel J.; Bergmann, Sven; Boerwinkle, Eric; Bottinger, Erwin P.; Campbell, Archie; Chakravarti, Aravinda; Chan, Yingleong; Chanock, Stephen J.; Chen, Constance; Chen, Y. D Ida; Collins, Francis S.; Connell, John; Correa, Adolfo; Cupples, L. Adrienne; Smith, George Davey; Davies, Gail; Dörr, Marcus; Ehret, Georg; Ellis, Stephen B.; Feenstra, Bjarke; Feitosa, Mary F.; Ford, Ian; Fox, Caroline S.; Frayling, Timothy M.; Friedrich, Nele; Geller, Frank; Scotland, Generation; Gillham-Nasenya, Irina; Gottesman, Omri; Graff, Misa; Grodstein, Francine; Gu, Charles; Haley, Chris; Hammond, Christopher J.; Harris, Sarah E.; Harris, Tamara B.; Hastie, Nicholas D.; Heard-Costa, Nancy L.; Heikkilä, Kauko; Hocking, Lynne J.; Homuth, Georg; Hottenga, Jouke Jan; Huang, Jinyan; Huffman, Jennifer E.; Hysi, Pirro G.; Ikram, M. Arfan; Ingelsson, Erik; Joensuu, Anni; Johansson, Åsa; Jousilahti, Pekka; Jukema, J. Wouter; Kähönen, Mika; Kamatani, Yoichiro; Kanoni, Stavroula; Kerr, Shona M.; Khan, Nazir M.; Koellinger, Philipp; Koistinen, Heikki A.; Kooner, Manraj K.; Kubo, Michiaki; Kuusisto, Johanna; Lahti, Jari; Launer, Lenore J.; Lea, Rodney A.; Lehne, Benjamin; Lehtimäki, Terho; Liewald, David C M; Lind, Lars; Loh, Marie; Lokki, Marja Liisa; London, Stephanie J.; Loomis, Stephanie J.; Loukola, Anu; Lu, Yingchang; Lumley, Thomas; Lundqvist, Annamari; Männistö, Satu; Marques-Vidal, Pedro; Masciullo, Corrado; Matchan, Angela; Mathias, Rasika A.; Matsuda, Koichi; Meigs, James B.; Meisinger, Christa; Meitinger, Thomas; Menni, Cristina; Mentch, Frank D.; Mihailov, Evelin; Milani, Lili; Montasser, May E.; Montgomery, Grant W.; Morrison, Alanna; Myers, Richard H.; Nadukuru, Rajiv; Navarro, Pau; Nalis, Mari; Nieminen, Markku S.; Nolte, Ilja M.; O'Connor, George T.; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R.; Pankow, James S.; Patarcic, Inga; Pavani, Francesca; Peyser, Patricia A.; Pietilainen, Kirsi; Poulter, Neil; Prokopenko, Inga; Ralhan, Sarju; Redmond, Paul; Rich, Stephen S.; Rissanen, Harri; Robino, Antonietta; Rose, Lynda M.; Rose, Richard; Sala, Cinzia; Salako, Babatunde; Salomaa, Veikko; Sarin, Antti Pekka; Saxena, Richa; Schmidt, Helena; Scott, Laura J.; Scott, William R.; Sennblad, Bengt; Seshadri, Sudha; Sever, Peter; Shrestha, Smeeta; Smith, Blair H.; Smith, Jennifer A.; Soranzo, Nicole; Sotoodehnia, Nona; Southam, Lorraine; Stanton, Alice V.; Stathopoulou, Maria G.; Strauch, Konstantin; Strawbridge, Rona J.; Suderman, Matthew J.; Tandon, Nikhil; Tang, Sian Tsun; Taylor, Kent D.; Tayo, Bamidele O.; Töglhofer, Anna Maria; Tomaszewski, Maciej; Tšernikova, Natalia; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Vaidya, Dhananjay; Van Hylckama Vlieg, Astrid; Van Setten, Jessica; Vasankari, Tuula; Vedantam, Sailaja; Vlachopoulou, Efthymia; Vozzi, Diego; Vuoksimaa, Eero; Waldenberger, Melanie; Ware, Erin B.; Wentworth-Shields, William; Whitfield, John B.; Wild, Sarah; Willemsen, Gonneke; Yajnik, Chittaranjan S.; Yao, Jie; Zaza, Gianluigi; Zhu, Xiaofeng; Salem, Rany M.; Melbye, Mads; Bisgaard, Hans; Samani, Nilesh J.; Cusi, Daniele; Mackey, David A.; Cooper, Richard S.; Froguel, Philippe; Pasterkamp, Gerard; Grant, Struan F A; Hakonarson, Hakon; Ferrucci, Luigi; Scott, Robert A.; Morris, Andrew D.; Palmer, Colin N A; Dedoussis, George; Deloukas, Panos; Bertram, Lars; Lindenberger, Ulman; Berndt, Sonja I.; Lindgren, Cecilia M.; Timpson, Nicholas J.; Tönjes, Anke; Munroe, Patricia B.; Sørensen, Thorkild I A; Rotimi, Charles N.; Arnett, Donna K.; Oldehinkel, Albertine J.; Kardia, Sharon L R; Balkau, Beverley; Gambaro, Giovanni; Morris, Andrew P.; Eriksson, Johan G.; Wright, Margie J.; Martin, Nicholas G.; Hunt, Steven C.; Starr, John M.; Deary, Ian J.; Griffiths, Lyn R.; Tiemeier, Henning; Pirastu, Nicola; Kaprio, Jaakko; Wareham, Nicholas J.; Pérusse, Louis; Wilson, James G.; Girotto, Giorgia; Caulfield, Mark J.; Raitakari, Olli; Boomsma, Dorret I.; Gieger, Christian; Van Der Harst, Pim; Hicks, Andrew A.; Kraft, Peter; Sinisalo, Juha; Knekt, Paul; Johannesson, Magnus; Magnusson, Patrik K E; Hamsten, Anders; Schmidt, Reinhold; Borecki, Ingrid B.; Vartiainen, Erkki; Becker, Diane M.; Bharadwaj, Dwaipayan; Mohlke, Karen L.; Boehnke, Michael; Van Duijn, Cornelia M.; Sanghera, Dharambir K.; Teumer, Alexander; Zeggini, Eleftheria; Metspalu, Andres; Gasparini, Paolo; Ulivi, Sheila; Ober, Carole; Toniolo, Daniela; Rudan, Igor; Porteous, David J.; Ciullo, Marina; Spector, Tim D.; Hayward, Caroline; Dupuis, Josée; Loos, Ruth J F; Wright, Alan F.; Chandak, Giriraj R.; Vollenweider, Peter; Shuldiner, Alan R.; Ridker, Paul M.; Rotter, Jerome I.; Sattar, Naveed; Gyllensten, Ulf; North, Kari E.; Pirastu, Mario; Psaty, Bruce M.; Weir, David R.; Laakso, Markku; Gudnason, Vilmundur; Takahashi, Atsushi; Chambers, John C.; Kooner, Jaspal S.; Strachan, David P.; Campbell, Harry; Hirschhorn, Joel N.; Perola, Markus; Polašek, Ozren; Wilson, James F.

In: Nature, Vol. 523, No. 7561, 23.07.2015, p. 459-462.

Research output: Contribution to journalArticle

Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AV, Zhang, W, Okada, Y, Stančáková, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MP, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, X, Chasman, DI, O'Connel, JR, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Traglia, M, Farmaki, AE, Kacprowski, T, Bjonnes, A, Van Der Spek, A, Wu, Y, Giri, AK, Yanek, LR, Wang, L, Hofer, E, Rietveld, CA, McLeod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, SS, Benton, MC, Broeckel, U, Medland, SE, Lind, PA, Malerba, G, Drong, A, Yengo, L, Bielak, LF, Zhi, D, Van Der Most, PJ, Shriner, D, Mägi, R, Hemani, G, Karaderi, T, Wang, Z, Liu, T, Demuth, I, Zhao, JH, Meng, W, Lataniotis, L, Van Der Laan, SW, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, LM, Salvi, E, Yazar, S, Carstensen, L, De Haan, HG, Abney, M, Afzal, U, Allison, MA, Amin, N, Asselbergs, FW, Bakker, SJL, Barr, RG, Baumeister, SE, Benjamin, DJ, Bergmann, S, Boerwinkle, E, Bottinger, EP, Campbell, A, Chakravarti, A, Chan, Y, Chanock, SJ, Chen, C, Chen, YDI, Collins, FS, Connell, J, Correa, A, Cupples, LA, Smith, GD, Davies, G, Dörr, M, Ehret, G, Ellis, SB, Feenstra, B, Feitosa, MF, Ford, I, Fox, CS, Frayling, TM, Friedrich, N, Geller, F, Scotland, G, Gillham-Nasenya, I, Gottesman, O, Graff, M, Grodstein, F, Gu, C, Haley, C, Hammond, CJ, Harris, SE, Harris, TB, Hastie, ND, Heard-Costa, NL, Heikkilä, K, Hocking, LJ, Homuth, G, Hottenga, JJ, Huang, J, Huffman, JE, Hysi, PG, Ikram, MA, Ingelsson, E, Joensuu, A, Johansson, Å, Jousilahti, P, Jukema, JW, Kähönen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, P, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, LJ, Lea, RA, Lehne, B, Lehtimäki, T, Liewald, DCM, Lind, L, Loh, M, Lokki, ML, London, SJ, Loomis, SJ, Loukola, A, Lu, Y, Lumley, T, Lundqvist, A, Männistö, S, Marques-Vidal, P, Masciullo, C, Matchan, A, Mathias, RA, Matsuda, K, Meigs, JB, Meisinger, C, Meitinger, T, Menni, C, Mentch, FD, Mihailov, E, Milani, L, Montasser, ME, Montgomery, GW, Morrison, A, Myers, RH, Nadukuru, R, Navarro, P, Nalis, M, Nieminen, MS, Nolte, IM, O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, WR, Pankow, JS, Patarcic, I, Pavani, F, Peyser, PA, Pietilainen, K, Poulter, N, Prokopenko, I, Ralhan, S, Redmond, P, Rich, SS, Rissanen, H, Robino, A, Rose, LM, Rose, R, Sala, C, Salako, B, Salomaa, V, Sarin, AP, Saxena, R, Schmidt, H, Scott, LJ, Scott, WR, Sennblad, B, Seshadri, S, Sever, P, Shrestha, S, Smith, BH, Smith, JA, Soranzo, N, Sotoodehnia, N, Southam, L, Stanton, AV, Stathopoulou, MG, Strauch, K, Strawbridge, RJ, Suderman, MJ, Tandon, N, Tang, ST, Taylor, KD, Tayo, BO, Töglhofer, AM, Tomaszewski, M, Tšernikova, N, Tuomilehto, J, Uitterlinden, AG, Vaidya, D, Van Hylckama Vlieg, A, Van Setten, J, Vasankari, T, Vedantam, S, Vlachopoulou, E, Vozzi, D, Vuoksimaa, E, Waldenberger, M, Ware, EB, Wentworth-Shields, W, Whitfield, JB, Wild, S, Willemsen, G, Yajnik, CS, Yao, J, Zaza, G, Zhu, X, Salem, RM, Melbye, M, Bisgaard, H, Samani, NJ, Cusi, D, Mackey, DA, Cooper, RS, Froguel, P, Pasterkamp, G, Grant, SFA, Hakonarson, H, Ferrucci, L, Scott, RA, Morris, AD, Palmer, CNA, Dedoussis, G, Deloukas, P, Bertram, L, Lindenberger, U, Berndt, SI, Lindgren, CM, Timpson, NJ, Tönjes, A, Munroe, PB, Sørensen, TIA, Rotimi, CN, Arnett, DK, Oldehinkel, AJ, Kardia, SLR, Balkau, B, Gambaro, G, Morris, AP, Eriksson, JG, Wright, MJ, Martin, NG, Hunt, SC, Starr, JM, Deary, IJ, Griffiths, LR, Tiemeier, H, Pirastu, N, Kaprio, J, Wareham, NJ, Pérusse, L, Wilson, JG, Girotto, G, Caulfield, MJ, Raitakari, O, Boomsma, DI, Gieger, C, Van Der Harst, P, Hicks, AA, Kraft, P, Sinisalo, J, Knekt, P, Johannesson, M, Magnusson, PKE, Hamsten, A, Schmidt, R, Borecki, IB, Vartiainen, E, Becker, DM, Bharadwaj, D, Mohlke, KL, Boehnke, M, Van Duijn, CM, Sanghera, DK, Teumer, A, Zeggini, E, Metspalu, A, Gasparini, P, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, DJ, Ciullo, M, Spector, TD, Hayward, C, Dupuis, J, Loos, RJF, Wright, AF, Chandak, GR, Vollenweider, P, Shuldiner, AR, Ridker, PM, Rotter, JI, Sattar, N, Gyllensten, U, North, KE, Pirastu, M, Psaty, BM, Weir, DR, Laakso, M, Gudnason, V, Takahashi, A, Chambers, JC, Kooner, JS, Strachan, DP, Campbell, H, Hirschhorn, JN, Perola, M, Polašek, O & Wilson, JF 2015, 'Directional dominance on stature and cognition in diverse human populations', Nature, vol. 523, no. 7561, pp. 459-462. https://doi.org/10.1038/nature14618
Joshi PK, Esko T, Mattsson H, Eklund N, Gandin I, Nutile T et al. Directional dominance on stature and cognition in diverse human populations. Nature. 2015 Jul 23;523(7561):459-462. https://doi.org/10.1038/nature14618
Joshi, Peter K. ; Esko, Tonu ; Mattsson, Hannele ; Eklund, Niina ; Gandin, Ilaria ; Nutile, Teresa ; Jackson, Anne U. ; Schurmann, Claudia ; Smith, Albert V. ; Zhang, Weihua ; Okada, Yukinori ; Stančáková, Alena ; Faul, Jessica D. ; Zhao, Wei ; Bartz, Traci M. ; Concas, Maria Pina ; Franceschini, Nora ; Enroth, Stefan ; Vitart, Veronique ; Trompet, Stella ; Guo, Xiuqing ; Chasman, Daniel I. ; O'Connel, Jeffrey R. ; Corre, Tanguy ; Nongmaithem, Suraj S. ; Chen, Yuning ; Mangino, Massimo ; Ruggiero, Daniela ; Traglia, Michela ; Farmaki, Aliki Eleni ; Kacprowski, Tim ; Bjonnes, Andrew ; Van Der Spek, Ashley ; Wu, Ying ; Giri, Anil K. ; Yanek, Lisa R. ; Wang, Lihua ; Hofer, Edith ; Rietveld, Cornelius A. ; McLeod, Olga ; Cornelis, Marilyn C. ; Pattaro, Cristian ; Verweij, Niek ; Baumbach, Clemens ; Abdellaoui, Abdel ; Warren, Helen R. ; Vuckovic, Dragana ; Mei, Hao ; Bouchard, Claude ; Perry, John R B ; Cappellani, Stefania ; Mirza, Saira S. ; Benton, Miles C. ; Broeckel, Ulrich ; Medland, Sarah E. ; Lind, Penelope A. ; Malerba, Giovanni ; Drong, Alexander ; Yengo, Loic ; Bielak, Lawrence F. ; Zhi, Degui ; Van Der Most, Peter J. ; Shriner, Daniel ; Mägi, Reedik ; Hemani, Gibran ; Karaderi, Tugce ; Wang, Zhaoming ; Liu, Tian ; Demuth, Ilja ; Zhao, Jing Hua ; Meng, Weihua ; Lataniotis, Lazaros ; Van Der Laan, Sander W. ; Bradfield, Jonathan P. ; Wood, Andrew R. ; Bonnefond, Amelie ; Ahluwalia, Tarunveer S. ; Hall, Leanne M. ; Salvi, Erika ; Yazar, Seyhan ; Carstensen, Lisbeth ; De Haan, Hugoline G. ; Abney, Mark ; Afzal, Uzma ; Allison, Matthew A. ; Amin, Najaf ; Asselbergs, Folkert W. ; Bakker, Stephan J L ; Barr, R. Graham ; Baumeister, Sebastian E. ; Benjamin, Daniel J. ; Bergmann, Sven ; Boerwinkle, Eric ; Bottinger, Erwin P. ; Campbell, Archie ; Chakravarti, Aravinda ; Chan, Yingleong ; Chanock, Stephen J. ; Chen, Constance ; Chen, Y. D Ida ; Collins, Francis S. ; Connell, John ; Correa, Adolfo ; Cupples, L. Adrienne ; Smith, George Davey ; Davies, Gail ; Dörr, Marcus ; Ehret, Georg ; Ellis, Stephen B. ; Feenstra, Bjarke ; Feitosa, Mary F. ; Ford, Ian ; Fox, Caroline S. ; Frayling, Timothy M. ; Friedrich, Nele ; Geller, Frank ; Scotland, Generation ; Gillham-Nasenya, Irina ; Gottesman, Omri ; Graff, Misa ; Grodstein, Francine ; Gu, Charles ; Haley, Chris ; Hammond, Christopher J. ; Harris, Sarah E. ; Harris, Tamara B. ; Hastie, Nicholas D. ; Heard-Costa, Nancy L. ; Heikkilä, Kauko ; Hocking, Lynne J. ; Homuth, Georg ; Hottenga, Jouke Jan ; Huang, Jinyan ; Huffman, Jennifer E. ; Hysi, Pirro G. ; Ikram, M. Arfan ; Ingelsson, Erik ; Joensuu, Anni ; Johansson, Åsa ; Jousilahti, Pekka ; Jukema, J. Wouter ; Kähönen, Mika ; Kamatani, Yoichiro ; Kanoni, Stavroula ; Kerr, Shona M. ; Khan, Nazir M. ; Koellinger, Philipp ; Koistinen, Heikki A. ; Kooner, Manraj K. ; Kubo, Michiaki ; Kuusisto, Johanna ; Lahti, Jari ; Launer, Lenore J. ; Lea, Rodney A. ; Lehne, Benjamin ; Lehtimäki, Terho ; Liewald, David C M ; Lind, Lars ; Loh, Marie ; Lokki, Marja Liisa ; London, Stephanie J. ; Loomis, Stephanie J. ; Loukola, Anu ; Lu, Yingchang ; Lumley, Thomas ; Lundqvist, Annamari ; Männistö, Satu ; Marques-Vidal, Pedro ; Masciullo, Corrado ; Matchan, Angela ; Mathias, Rasika A. ; Matsuda, Koichi ; Meigs, James B. ; Meisinger, Christa ; Meitinger, Thomas ; Menni, Cristina ; Mentch, Frank D. ; Mihailov, Evelin ; Milani, Lili ; Montasser, May E. ; Montgomery, Grant W. ; Morrison, Alanna ; Myers, Richard H. ; Nadukuru, Rajiv ; Navarro, Pau ; Nalis, Mari ; Nieminen, Markku S. ; Nolte, Ilja M. ; O'Connor, George T. ; Ogunniyi, Adesola ; Padmanabhan, Sandosh ; Palmas, Walter R. ; Pankow, James S. ; Patarcic, Inga ; Pavani, Francesca ; Peyser, Patricia A. ; Pietilainen, Kirsi ; Poulter, Neil ; Prokopenko, Inga ; Ralhan, Sarju ; Redmond, Paul ; Rich, Stephen S. ; Rissanen, Harri ; Robino, Antonietta ; Rose, Lynda M. ; Rose, Richard ; Sala, Cinzia ; Salako, Babatunde ; Salomaa, Veikko ; Sarin, Antti Pekka ; Saxena, Richa ; Schmidt, Helena ; Scott, Laura J. ; Scott, William R. ; Sennblad, Bengt ; Seshadri, Sudha ; Sever, Peter ; Shrestha, Smeeta ; Smith, Blair H. ; Smith, Jennifer A. ; Soranzo, Nicole ; Sotoodehnia, Nona ; Southam, Lorraine ; Stanton, Alice V. ; Stathopoulou, Maria G. ; Strauch, Konstantin ; Strawbridge, Rona J. ; Suderman, Matthew J. ; Tandon, Nikhil ; Tang, Sian Tsun ; Taylor, Kent D. ; Tayo, Bamidele O. ; Töglhofer, Anna Maria ; Tomaszewski, Maciej ; Tšernikova, Natalia ; Tuomilehto, Jaakko ; Uitterlinden, Andre G. ; Vaidya, Dhananjay ; Van Hylckama Vlieg, Astrid ; Van Setten, Jessica ; Vasankari, Tuula ; Vedantam, Sailaja ; Vlachopoulou, Efthymia ; Vozzi, Diego ; Vuoksimaa, Eero ; Waldenberger, Melanie ; Ware, Erin B. ; Wentworth-Shields, William ; Whitfield, John B. ; Wild, Sarah ; Willemsen, Gonneke ; Yajnik, Chittaranjan S. ; Yao, Jie ; Zaza, Gianluigi ; Zhu, Xiaofeng ; Salem, Rany M. ; Melbye, Mads ; Bisgaard, Hans ; Samani, Nilesh J. ; Cusi, Daniele ; Mackey, David A. ; Cooper, Richard S. ; Froguel, Philippe ; Pasterkamp, Gerard ; Grant, Struan F A ; Hakonarson, Hakon ; Ferrucci, Luigi ; Scott, Robert A. ; Morris, Andrew D. ; Palmer, Colin N A ; Dedoussis, George ; Deloukas, Panos ; Bertram, Lars ; Lindenberger, Ulman ; Berndt, Sonja I. ; Lindgren, Cecilia M. ; Timpson, Nicholas J. ; Tönjes, Anke ; Munroe, Patricia B. ; Sørensen, Thorkild I A ; Rotimi, Charles N. ; Arnett, Donna K. ; Oldehinkel, Albertine J. ; Kardia, Sharon L R ; Balkau, Beverley ; Gambaro, Giovanni ; Morris, Andrew P. ; Eriksson, Johan G. ; Wright, Margie J. ; Martin, Nicholas G. ; Hunt, Steven C. ; Starr, John M. ; Deary, Ian J. ; Griffiths, Lyn R. ; Tiemeier, Henning ; Pirastu, Nicola ; Kaprio, Jaakko ; Wareham, Nicholas J. ; Pérusse, Louis ; Wilson, James G. ; Girotto, Giorgia ; Caulfield, Mark J. ; Raitakari, Olli ; Boomsma, Dorret I. ; Gieger, Christian ; Van Der Harst, Pim ; Hicks, Andrew A. ; Kraft, Peter ; Sinisalo, Juha ; Knekt, Paul ; Johannesson, Magnus ; Magnusson, Patrik K E ; Hamsten, Anders ; Schmidt, Reinhold ; Borecki, Ingrid B. ; Vartiainen, Erkki ; Becker, Diane M. ; Bharadwaj, Dwaipayan ; Mohlke, Karen L. ; Boehnke, Michael ; Van Duijn, Cornelia M. ; Sanghera, Dharambir K. ; Teumer, Alexander ; Zeggini, Eleftheria ; Metspalu, Andres ; Gasparini, Paolo ; Ulivi, Sheila ; Ober, Carole ; Toniolo, Daniela ; Rudan, Igor ; Porteous, David J. ; Ciullo, Marina ; Spector, Tim D. ; Hayward, Caroline ; Dupuis, Josée ; Loos, Ruth J F ; Wright, Alan F. ; Chandak, Giriraj R. ; Vollenweider, Peter ; Shuldiner, Alan R. ; Ridker, Paul M. ; Rotter, Jerome I. ; Sattar, Naveed ; Gyllensten, Ulf ; North, Kari E. ; Pirastu, Mario ; Psaty, Bruce M. ; Weir, David R. ; Laakso, Markku ; Gudnason, Vilmundur ; Takahashi, Atsushi ; Chambers, John C. ; Kooner, Jaspal S. ; Strachan, David P. ; Campbell, Harry ; Hirschhorn, Joel N. ; Perola, Markus ; Polašek, Ozren ; Wilson, James F. / Directional dominance on stature and cognition in diverse human populations. In: Nature. 2015 ; Vol. 523, No. 7561. pp. 459-462.
@article{7cad7540cb8546d58be399bad174995c,
title = "Directional dominance on stature and cognition in diverse human populations",
abstract = "Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P <1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.",
author = "Joshi, {Peter K.} and Tonu Esko and Hannele Mattsson and Niina Eklund and Ilaria Gandin and Teresa Nutile and Jackson, {Anne U.} and Claudia Schurmann and Smith, {Albert V.} and Weihua Zhang and Yukinori Okada and Alena Stanč{\'a}kov{\'a} and Faul, {Jessica D.} and Wei Zhao and Bartz, {Traci M.} and Concas, {Maria Pina} and Nora Franceschini and Stefan Enroth and Veronique Vitart and Stella Trompet and Xiuqing Guo and Chasman, {Daniel I.} and O'Connel, {Jeffrey R.} and Tanguy Corre and Nongmaithem, {Suraj S.} and Yuning Chen and Massimo Mangino and Daniela Ruggiero and Michela Traglia and Farmaki, {Aliki Eleni} and Tim Kacprowski and Andrew Bjonnes and {Van Der Spek}, Ashley and Ying Wu and Giri, {Anil K.} and Yanek, {Lisa R.} and Lihua Wang and Edith Hofer and Rietveld, {Cornelius A.} and Olga McLeod and Cornelis, {Marilyn C.} and Cristian Pattaro and Niek Verweij and Clemens Baumbach and Abdel Abdellaoui and Warren, {Helen R.} and Dragana Vuckovic and Hao Mei and Claude Bouchard and Perry, {John R B} and Stefania Cappellani and Mirza, {Saira S.} and Benton, {Miles C.} and Ulrich Broeckel and Medland, {Sarah E.} and Lind, {Penelope A.} and Giovanni Malerba and Alexander Drong and Loic Yengo and Bielak, {Lawrence F.} and Degui Zhi and {Van Der Most}, {Peter J.} and Daniel Shriner and Reedik M{\"a}gi and Gibran Hemani and Tugce Karaderi and Zhaoming Wang and Tian Liu and Ilja Demuth and Zhao, {Jing Hua} and Weihua Meng and Lazaros Lataniotis and {Van Der Laan}, {Sander W.} and Bradfield, {Jonathan P.} and Wood, {Andrew R.} and Amelie Bonnefond and Ahluwalia, {Tarunveer S.} and Hall, {Leanne M.} and Erika Salvi and Seyhan Yazar and Lisbeth Carstensen and {De Haan}, {Hugoline G.} and Mark Abney and Uzma Afzal and Allison, {Matthew A.} and Najaf Amin and Asselbergs, {Folkert W.} and Bakker, {Stephan J L} and Barr, {R. Graham} and Baumeister, {Sebastian E.} and Benjamin, {Daniel J.} and Sven Bergmann and Eric Boerwinkle and Bottinger, {Erwin P.} and Archie Campbell and Aravinda Chakravarti and Yingleong Chan and Chanock, {Stephen J.} and Constance Chen and Chen, {Y. D Ida} and Collins, {Francis S.} and John Connell and Adolfo Correa and Cupples, {L. Adrienne} and Smith, {George Davey} and Gail Davies and Marcus D{\"o}rr and Georg Ehret and Ellis, {Stephen B.} and Bjarke Feenstra and Feitosa, {Mary F.} and Ian Ford and Fox, {Caroline S.} and Frayling, {Timothy M.} and Nele Friedrich and Frank Geller and Generation Scotland and Irina Gillham-Nasenya and Omri Gottesman and Misa Graff and Francine Grodstein and Charles Gu and Chris Haley and Hammond, {Christopher J.} and Harris, {Sarah E.} and Harris, {Tamara B.} and Hastie, {Nicholas D.} and Heard-Costa, {Nancy L.} and Kauko Heikkil{\"a} and Hocking, {Lynne J.} and Georg Homuth and Hottenga, {Jouke Jan} and Jinyan Huang and Huffman, {Jennifer E.} and Hysi, {Pirro G.} and Ikram, {M. Arfan} and Erik Ingelsson and Anni Joensuu and {\AA}sa Johansson and Pekka Jousilahti and Jukema, {J. Wouter} and Mika K{\"a}h{\"o}nen and Yoichiro Kamatani and Stavroula Kanoni and Kerr, {Shona M.} and Khan, {Nazir M.} and Philipp Koellinger and Koistinen, {Heikki A.} and Kooner, {Manraj K.} and Michiaki Kubo and Johanna Kuusisto and Jari Lahti and Launer, {Lenore J.} and Lea, {Rodney A.} and Benjamin Lehne and Terho Lehtim{\"a}ki and Liewald, {David C M} and Lars Lind and Marie Loh and Lokki, {Marja Liisa} and London, {Stephanie J.} and Loomis, {Stephanie J.} and Anu Loukola and Yingchang Lu and Thomas Lumley and Annamari Lundqvist and Satu M{\"a}nnist{\"o} and Pedro Marques-Vidal and Corrado Masciullo and Angela Matchan and Mathias, {Rasika A.} and Koichi Matsuda and Meigs, {James B.} and Christa Meisinger and Thomas Meitinger and Cristina Menni and Mentch, {Frank D.} and Evelin Mihailov and Lili Milani and Montasser, {May E.} and Montgomery, {Grant W.} and Alanna Morrison and Myers, {Richard H.} and Rajiv Nadukuru and Pau Navarro and Mari Nalis and Nieminen, {Markku S.} and Nolte, {Ilja M.} and O'Connor, {George T.} and Adesola Ogunniyi and Sandosh Padmanabhan and Palmas, {Walter R.} and Pankow, {James S.} and Inga Patarcic and Francesca Pavani and Peyser, {Patricia A.} and Kirsi Pietilainen and Neil Poulter and Inga Prokopenko and Sarju Ralhan and Paul Redmond and Rich, {Stephen S.} and Harri Rissanen and Antonietta Robino and Rose, {Lynda M.} and Richard Rose and Cinzia Sala and Babatunde Salako and Veikko Salomaa and Sarin, {Antti Pekka} and Richa Saxena and Helena Schmidt and Scott, {Laura J.} and Scott, {William R.} and Bengt Sennblad and Sudha Seshadri and Peter Sever and Smeeta Shrestha and Smith, {Blair H.} and Smith, {Jennifer A.} and Nicole Soranzo and Nona Sotoodehnia and Lorraine Southam and Stanton, {Alice V.} and Stathopoulou, {Maria G.} and Konstantin Strauch and Strawbridge, {Rona J.} and Suderman, {Matthew J.} and Nikhil Tandon and Tang, {Sian Tsun} and Taylor, {Kent D.} and Tayo, {Bamidele O.} and T{\"o}glhofer, {Anna Maria} and Maciej Tomaszewski and Natalia Tšernikova and Jaakko Tuomilehto and Uitterlinden, {Andre G.} and Dhananjay Vaidya and {Van Hylckama Vlieg}, Astrid and {Van Setten}, Jessica and Tuula Vasankari and Sailaja Vedantam and Efthymia Vlachopoulou and Diego Vozzi and Eero Vuoksimaa and Melanie Waldenberger and Ware, {Erin B.} and William Wentworth-Shields and Whitfield, {John B.} and Sarah Wild and Gonneke Willemsen and Yajnik, {Chittaranjan S.} and Jie Yao and Gianluigi Zaza and Xiaofeng Zhu and Salem, {Rany M.} and Mads Melbye and Hans Bisgaard and Samani, {Nilesh J.} and Daniele Cusi and Mackey, {David A.} and Cooper, {Richard S.} and Philippe Froguel and Gerard Pasterkamp and Grant, {Struan F A} and Hakon Hakonarson and Luigi Ferrucci and Scott, {Robert A.} and Morris, {Andrew D.} and Palmer, {Colin N A} and George Dedoussis and Panos Deloukas and Lars Bertram and Ulman Lindenberger and Berndt, {Sonja I.} and Lindgren, {Cecilia M.} and Timpson, {Nicholas J.} and Anke T{\"o}njes and Munroe, {Patricia B.} and S{\o}rensen, {Thorkild I A} and Rotimi, {Charles N.} and Arnett, {Donna K.} and Oldehinkel, {Albertine J.} and Kardia, {Sharon L R} and Beverley Balkau and Giovanni Gambaro and Morris, {Andrew P.} and Eriksson, {Johan G.} and Wright, {Margie J.} and Martin, {Nicholas G.} and Hunt, {Steven C.} and Starr, {John M.} and Deary, {Ian J.} and Griffiths, {Lyn R.} and Henning Tiemeier and Nicola Pirastu and Jaakko Kaprio and Wareham, {Nicholas J.} and Louis P{\'e}russe and Wilson, {James G.} and Giorgia Girotto and Caulfield, {Mark J.} and Olli Raitakari and Boomsma, {Dorret I.} and Christian Gieger and {Van Der Harst}, Pim and Hicks, {Andrew A.} and Peter Kraft and Juha Sinisalo and Paul Knekt and Magnus Johannesson and Magnusson, {Patrik K E} and Anders Hamsten and Reinhold Schmidt and Borecki, {Ingrid B.} and Erkki Vartiainen and Becker, {Diane M.} and Dwaipayan Bharadwaj and Mohlke, {Karen L.} and Michael Boehnke and {Van Duijn}, {Cornelia M.} and Sanghera, {Dharambir K.} and Alexander Teumer and Eleftheria Zeggini and Andres Metspalu and Paolo Gasparini and Sheila Ulivi and Carole Ober and Daniela Toniolo and Igor Rudan and Porteous, {David J.} and Marina Ciullo and Spector, {Tim D.} and Caroline Hayward and Jos{\'e}e Dupuis and Loos, {Ruth J F} and Wright, {Alan F.} and Chandak, {Giriraj R.} and Peter Vollenweider and Shuldiner, {Alan R.} and Ridker, {Paul M.} and Rotter, {Jerome I.} and Naveed Sattar and Ulf Gyllensten and North, {Kari E.} and Mario Pirastu and Psaty, {Bruce M.} and Weir, {David R.} and Markku Laakso and Vilmundur Gudnason and Atsushi Takahashi and Chambers, {John C.} and Kooner, {Jaspal S.} and Strachan, {David P.} and Harry Campbell and Hirschhorn, {Joel N.} and Markus Perola and Ozren Polašek and Wilson, {James F.}",
year = "2015",
month = "7",
day = "23",
doi = "10.1038/nature14618",
language = "English",
volume = "523",
pages = "459--462",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7561",

}

TY - JOUR

T1 - Directional dominance on stature and cognition in diverse human populations

AU - Joshi, Peter K.

AU - Esko, Tonu

AU - Mattsson, Hannele

AU - Eklund, Niina

AU - Gandin, Ilaria

AU - Nutile, Teresa

AU - Jackson, Anne U.

AU - Schurmann, Claudia

AU - Smith, Albert V.

AU - Zhang, Weihua

AU - Okada, Yukinori

AU - Stančáková, Alena

AU - Faul, Jessica D.

AU - Zhao, Wei

AU - Bartz, Traci M.

AU - Concas, Maria Pina

AU - Franceschini, Nora

AU - Enroth, Stefan

AU - Vitart, Veronique

AU - Trompet, Stella

AU - Guo, Xiuqing

AU - Chasman, Daniel I.

AU - O'Connel, Jeffrey R.

AU - Corre, Tanguy

AU - Nongmaithem, Suraj S.

AU - Chen, Yuning

AU - Mangino, Massimo

AU - Ruggiero, Daniela

AU - Traglia, Michela

AU - Farmaki, Aliki Eleni

AU - Kacprowski, Tim

AU - Bjonnes, Andrew

AU - Van Der Spek, Ashley

AU - Wu, Ying

AU - Giri, Anil K.

AU - Yanek, Lisa R.

AU - Wang, Lihua

AU - Hofer, Edith

AU - Rietveld, Cornelius A.

AU - McLeod, Olga

AU - Cornelis, Marilyn C.

AU - Pattaro, Cristian

AU - Verweij, Niek

AU - Baumbach, Clemens

AU - Abdellaoui, Abdel

AU - Warren, Helen R.

AU - Vuckovic, Dragana

AU - Mei, Hao

AU - Bouchard, Claude

AU - Perry, John R B

AU - Cappellani, Stefania

AU - Mirza, Saira S.

AU - Benton, Miles C.

AU - Broeckel, Ulrich

AU - Medland, Sarah E.

AU - Lind, Penelope A.

AU - Malerba, Giovanni

AU - Drong, Alexander

AU - Yengo, Loic

AU - Bielak, Lawrence F.

AU - Zhi, Degui

AU - Van Der Most, Peter J.

AU - Shriner, Daniel

AU - Mägi, Reedik

AU - Hemani, Gibran

AU - Karaderi, Tugce

AU - Wang, Zhaoming

AU - Liu, Tian

AU - Demuth, Ilja

AU - Zhao, Jing Hua

AU - Meng, Weihua

AU - Lataniotis, Lazaros

AU - Van Der Laan, Sander W.

AU - Bradfield, Jonathan P.

AU - Wood, Andrew R.

AU - Bonnefond, Amelie

AU - Ahluwalia, Tarunveer S.

AU - Hall, Leanne M.

AU - Salvi, Erika

AU - Yazar, Seyhan

AU - Carstensen, Lisbeth

AU - De Haan, Hugoline G.

AU - Abney, Mark

AU - Afzal, Uzma

AU - Allison, Matthew A.

AU - Amin, Najaf

AU - Asselbergs, Folkert W.

AU - Bakker, Stephan J L

AU - Barr, R. Graham

AU - Baumeister, Sebastian E.

AU - Benjamin, Daniel J.

AU - Bergmann, Sven

AU - Boerwinkle, Eric

AU - Bottinger, Erwin P.

AU - Campbell, Archie

AU - Chakravarti, Aravinda

AU - Chan, Yingleong

AU - Chanock, Stephen J.

AU - Chen, Constance

AU - Chen, Y. D Ida

AU - Collins, Francis S.

AU - Connell, John

AU - Correa, Adolfo

AU - Cupples, L. Adrienne

AU - Smith, George Davey

AU - Davies, Gail

AU - Dörr, Marcus

AU - Ehret, Georg

AU - Ellis, Stephen B.

AU - Feenstra, Bjarke

AU - Feitosa, Mary F.

AU - Ford, Ian

AU - Fox, Caroline S.

AU - Frayling, Timothy M.

AU - Friedrich, Nele

AU - Geller, Frank

AU - Scotland, Generation

AU - Gillham-Nasenya, Irina

AU - Gottesman, Omri

AU - Graff, Misa

AU - Grodstein, Francine

AU - Gu, Charles

AU - Haley, Chris

AU - Hammond, Christopher J.

AU - Harris, Sarah E.

AU - Harris, Tamara B.

AU - Hastie, Nicholas D.

AU - Heard-Costa, Nancy L.

AU - Heikkilä, Kauko

AU - Hocking, Lynne J.

AU - Homuth, Georg

AU - Hottenga, Jouke Jan

AU - Huang, Jinyan

AU - Huffman, Jennifer E.

AU - Hysi, Pirro G.

AU - Ikram, M. Arfan

AU - Ingelsson, Erik

AU - Joensuu, Anni

AU - Johansson, Åsa

AU - Jousilahti, Pekka

AU - Jukema, J. Wouter

AU - Kähönen, Mika

AU - Kamatani, Yoichiro

AU - Kanoni, Stavroula

AU - Kerr, Shona M.

AU - Khan, Nazir M.

AU - Koellinger, Philipp

AU - Koistinen, Heikki A.

AU - Kooner, Manraj K.

AU - Kubo, Michiaki

AU - Kuusisto, Johanna

AU - Lahti, Jari

AU - Launer, Lenore J.

AU - Lea, Rodney A.

AU - Lehne, Benjamin

AU - Lehtimäki, Terho

AU - Liewald, David C M

AU - Lind, Lars

AU - Loh, Marie

AU - Lokki, Marja Liisa

AU - London, Stephanie J.

AU - Loomis, Stephanie J.

AU - Loukola, Anu

AU - Lu, Yingchang

AU - Lumley, Thomas

AU - Lundqvist, Annamari

AU - Männistö, Satu

AU - Marques-Vidal, Pedro

AU - Masciullo, Corrado

AU - Matchan, Angela

AU - Mathias, Rasika A.

AU - Matsuda, Koichi

AU - Meigs, James B.

AU - Meisinger, Christa

AU - Meitinger, Thomas

AU - Menni, Cristina

AU - Mentch, Frank D.

AU - Mihailov, Evelin

AU - Milani, Lili

AU - Montasser, May E.

AU - Montgomery, Grant W.

AU - Morrison, Alanna

AU - Myers, Richard H.

AU - Nadukuru, Rajiv

AU - Navarro, Pau

AU - Nalis, Mari

AU - Nieminen, Markku S.

AU - Nolte, Ilja M.

AU - O'Connor, George T.

AU - Ogunniyi, Adesola

AU - Padmanabhan, Sandosh

AU - Palmas, Walter R.

AU - Pankow, James S.

AU - Patarcic, Inga

AU - Pavani, Francesca

AU - Peyser, Patricia A.

AU - Pietilainen, Kirsi

AU - Poulter, Neil

AU - Prokopenko, Inga

AU - Ralhan, Sarju

AU - Redmond, Paul

AU - Rich, Stephen S.

AU - Rissanen, Harri

AU - Robino, Antonietta

AU - Rose, Lynda M.

AU - Rose, Richard

AU - Sala, Cinzia

AU - Salako, Babatunde

AU - Salomaa, Veikko

AU - Sarin, Antti Pekka

AU - Saxena, Richa

AU - Schmidt, Helena

AU - Scott, Laura J.

AU - Scott, William R.

AU - Sennblad, Bengt

AU - Seshadri, Sudha

AU - Sever, Peter

AU - Shrestha, Smeeta

AU - Smith, Blair H.

AU - Smith, Jennifer A.

AU - Soranzo, Nicole

AU - Sotoodehnia, Nona

AU - Southam, Lorraine

AU - Stanton, Alice V.

AU - Stathopoulou, Maria G.

AU - Strauch, Konstantin

AU - Strawbridge, Rona J.

AU - Suderman, Matthew J.

AU - Tandon, Nikhil

AU - Tang, Sian Tsun

AU - Taylor, Kent D.

AU - Tayo, Bamidele O.

AU - Töglhofer, Anna Maria

AU - Tomaszewski, Maciej

AU - Tšernikova, Natalia

AU - Tuomilehto, Jaakko

AU - Uitterlinden, Andre G.

AU - Vaidya, Dhananjay

AU - Van Hylckama Vlieg, Astrid

AU - Van Setten, Jessica

AU - Vasankari, Tuula

AU - Vedantam, Sailaja

AU - Vlachopoulou, Efthymia

AU - Vozzi, Diego

AU - Vuoksimaa, Eero

AU - Waldenberger, Melanie

AU - Ware, Erin B.

AU - Wentworth-Shields, William

AU - Whitfield, John B.

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AU - Magnusson, Patrik K E

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AU - Borecki, Ingrid B.

AU - Vartiainen, Erkki

AU - Becker, Diane M.

AU - Bharadwaj, Dwaipayan

AU - Mohlke, Karen L.

AU - Boehnke, Michael

AU - Van Duijn, Cornelia M.

AU - Sanghera, Dharambir K.

AU - Teumer, Alexander

AU - Zeggini, Eleftheria

AU - Metspalu, Andres

AU - Gasparini, Paolo

AU - Ulivi, Sheila

AU - Ober, Carole

AU - Toniolo, Daniela

AU - Rudan, Igor

AU - Porteous, David J.

AU - Ciullo, Marina

AU - Spector, Tim D.

AU - Hayward, Caroline

AU - Dupuis, Josée

AU - Loos, Ruth J F

AU - Wright, Alan F.

AU - Chandak, Giriraj R.

AU - Vollenweider, Peter

AU - Shuldiner, Alan R.

AU - Ridker, Paul M.

AU - Rotter, Jerome I.

AU - Sattar, Naveed

AU - Gyllensten, Ulf

AU - North, Kari E.

AU - Pirastu, Mario

AU - Psaty, Bruce M.

AU - Weir, David R.

AU - Laakso, Markku

AU - Gudnason, Vilmundur

AU - Takahashi, Atsushi

AU - Chambers, John C.

AU - Kooner, Jaspal S.

AU - Strachan, David P.

AU - Campbell, Harry

AU - Hirschhorn, Joel N.

AU - Perola, Markus

AU - Polašek, Ozren

AU - Wilson, James F.

PY - 2015/7/23

Y1 - 2015/7/23

N2 - Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P <1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

AB - Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P <1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

UR - http://www.scopus.com/inward/record.url?scp=84937889764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937889764&partnerID=8YFLogxK

U2 - 10.1038/nature14618

DO - 10.1038/nature14618

M3 - Article

VL - 523

SP - 459

EP - 462

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7561

ER -