Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney

LV Wain, A Vaez, R Jansen, R Joehanes, PJ Van Der Most, AM Erzurumluoglu, PF O'Reilly, CP Cabrera, HR Warren, LM Rose, GC Verwoert, JJ Hottenga, RJ Strawbridge, T Esko, DE Arking, SJ Hwang, X Guo, Z Kutalik, S Trompet, N ShrineA Teumer, JS Ried, JC Bis, AV Smith, N Amin, IM Nolte, LP Lyytikäinen, A Mahajan, NJ Wareham, E Hofer, PK Joshi, K Kristiansson, M Traglia, AS Havulinna, A Goel, MA Nalls, S Sõber, D Vuckovic, J Luan, FM Del Greco, KL Ayers, J Marrugat, D Ruggiero, LM Lopez, T Niiranen, S Enroth, AU Jackson, CP Nelson, JE Huffman, W Zhang, J Marten, I Gandin, SE Harris, T Zemunik, Y Lu, E Evangelou, N Shah, MH De Borst, M Mangino, BP Prins, A Campbell, R Li-Gao, G Chauhan, C Oldmeadow, G Abecasis, M Abedi, CM Barbieri, MR Barnes, C Batini, J Beilby, BIOS Consortium, T Blake, M Boehnke, EP Bottinger, PS Braund, M Brown, M Brumat, H Campbell, JC Chambers, M Cocca, F Collins, J Connell, HJ Cordell, JJ Damman, G Davies, EJ de Geus, R de Mutsert, J Deelen, Y Demirkale, ASF Doney, M Dörr, M Farrall, T Ferreira, M Frånberg, H Gao, V Giedraitis, C Gieger, F Giulianini, AJ Gow, A Hamsten, TB Harris, A Hofman, EG Holliday, J Hui, MR Jarvelin, Å Johansson, AD Johnson, P Jousilahti, A Jula, M Kähönen, S Kathiresan, KT Khaw, I Kolcic, S Koskinen, C Langenberg, M Larson, LJ Launer, B Lehne, DCM Liewald, L Lin, L Lind, F Mach, C Mamasoula, C Menni, B Mifsud, Y Milaneschi, A Morgan, AD Morris, AC Morrison, PJ Munson, P Nandakumar, QT Nguyen, T Nutile, AJ Oldehinkel, BA Oostra, E Org, S Padmanabhan, A Palotie, G Paré, A Pattie, BWJH Penninx, N Poulter, PP Pramstaller, OT Raitakari, M Ren, K Rice, PM Ridker, H Riese, S Ripatti, A Robino, JI Rotter, I Rudan, Y Saba, A Saint Pierre, CF Sala, AP Sarin, R Schmidt, R Scott, MA Seelen, DC Shields, D Siscovick, R Sorice, A Stanton, DJ Stott, J Sundström, M Swertz, KD Taylor, S Thom, I Tzoulaki, C Tzourio, AG Uitterlinden, U Völker, P Vollenweider, S Wild, G Willemsen, AF Wright, J Yao, S Thériault, D Conen, J Attia, P Sever, S Debette, DO Mook-Kanamori, E Zeggini, TD Spector, P van der Harst, CNA Palmer, AC Vergnaud, RJF Loos, O Polasek, JM Starr, G Girotto, C Hayward, JS Kooner, CM Lindgren, V Vitart, NJ Samani, J Tuomilehto, U Gyllensten, P Knekt, IJ Deary, M Ciullo, R Elosua, BD Keavney, AA Hicks, RA Scott, P Gasparini, M Laan, Y Liu, H Watkins, CA Hartman, V Salomaa, D Toniolo, M Perola, JF Wilson, H Schmidt, JH Zhao, T Lehtimäki, van Duijn CM, V Gudnason, BM Psaty, A Peters, R Rettig, A James, JW Jukema, DP Strachan, W Palmas, A Metspalu, E Ingelsson, DI Boomsma, OH Franco, M Bochud, C Newton-Cheh, PB Munroe, P Elliott, DI Chasman, A Chakravarti, J Knight, AP Morris, D Levy, MD Tobin, H Snieder, MJ Caulfield, GB Ehret

Research output: Contribution to journalArticle

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Abstract

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation. © 2017 American Heart Association, Inc.
Original languageEnglish
Pages (from-to)e4-e19
JournalHypertension
Volume70
Issue number3
DOIs
Publication statusPublished - 2017

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Genome-Wide Association Study
Genetic Association Studies
Blood Pressure
Kidney
Genes
Cardiovascular Diseases
Genome
Pharmacology
Hypertension
Gene Expression
Datasets
Therapeutics

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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney. / Wain, LV; Vaez, A; Jansen, R; Joehanes, R; Van Der Most, PJ; Erzurumluoglu, AM; O'Reilly, PF; Cabrera, CP; Warren, HR; Rose, LM; Verwoert, GC; Hottenga, JJ; Strawbridge, RJ; Esko, T; Arking, DE; Hwang, SJ; Guo, X; Kutalik, Z; Trompet, S; Shrine, N; Teumer, A; Ried, JS; Bis, JC; Smith, AV; Amin, N; Nolte, IM; Lyytikäinen, LP; Mahajan, A; Wareham, NJ; Hofer, E; Joshi, PK; Kristiansson, K; Traglia, M; Havulinna, AS; Goel, A; Nalls, MA; Sõber, S; Vuckovic, D; Luan, J; Del Greco, FM; Ayers, KL; Marrugat, J; Ruggiero, D; Lopez, LM; Niiranen, T; Enroth, S; Jackson, AU; Nelson, CP; Huffman, JE; Zhang, W; Marten, J; Gandin, I; Harris, SE; Zemunik, T; Lu, Y; Evangelou, E; Shah, N; De Borst, MH; Mangino, M; Prins, BP; Campbell, A; Li-Gao, R; Chauhan, G; Oldmeadow, C; Abecasis, G; Abedi, M; Barbieri, CM; Barnes, MR; Batini, C; Beilby, J; Consortium, BIOS; Blake, T; Boehnke, M; Bottinger, EP; Braund, PS; Brown, M; Brumat, M; Campbell, H; Chambers, JC; Cocca, M; Collins, F; Connell, J; Cordell, HJ; Damman, JJ; Davies, G; de Geus, EJ; de Mutsert, R; Deelen, J; Demirkale, Y; Doney, ASF; Dörr, M; Farrall, M; Ferreira, T; Frånberg, M; Gao, H; Giedraitis, V; Gieger, C; Giulianini, F; Gow, AJ; Hamsten, A; Harris, TB; Hofman, A; Holliday, EG; Hui, J; Jarvelin, MR; Johansson, Å; Johnson, AD; Jousilahti, P; Jula, A; Kähönen, M; Kathiresan, S; Khaw, KT; Kolcic, I; Koskinen, S; Langenberg, C; Larson, M; Launer, LJ; Lehne, B; Liewald, DCM; Lin, L; Lind, L; Mach, F; Mamasoula, C; Menni, C; Mifsud, B; Milaneschi, Y; Morgan, A; Morris, AD; Morrison, AC; Munson, PJ; Nandakumar, P; Nguyen, QT; Nutile, T; Oldehinkel, AJ; Oostra, BA; Org, E; Padmanabhan, S; Palotie, A; Paré, G; Pattie, A; Penninx, BWJH; Poulter, N; Pramstaller, PP; Raitakari, OT; Ren, M; Rice, K; Ridker, PM; Riese, H; Ripatti, S; Robino, A; Rotter, JI; Rudan, I; Saba, Y; Saint Pierre, A; Sala, CF; Sarin, AP; Schmidt, R; Scott, R; Seelen, MA; Shields, DC; Siscovick, D; Sorice, R; Stanton, A; Stott, DJ; Sundström, J; Swertz, M; Taylor, KD; Thom, S; Tzoulaki, I; Tzourio, C; Uitterlinden, AG; Völker, U; Vollenweider, P; Wild, S; Willemsen, G; Wright, AF; Yao, J; Thériault, S; Conen, D; Attia, J; Sever, P; Debette, S; Mook-Kanamori, DO; Zeggini, E; Spector, TD; van der Harst, P; Palmer, CNA; Vergnaud, AC; Loos, RJF; Polasek, O; Starr, JM; Girotto, G; Hayward, C; Kooner, JS; Lindgren, CM; Vitart, V; Samani, NJ; Tuomilehto, J; Gyllensten, U; Knekt, P; Deary, IJ; Ciullo, M; Elosua, R; Keavney, BD; Hicks, AA; Scott, RA; Gasparini, P; Laan, M; Liu, Y; Watkins, H; Hartman, CA; Salomaa, V; Toniolo, D; Perola, M; Wilson, JF; Schmidt, H; Zhao, JH; Lehtimäki, T; CM, van Duijn; Gudnason, V; Psaty, BM; Peters, A; Rettig, R; James, A; Jukema, JW; Strachan, DP; Palmas, W; Metspalu, A; Ingelsson, E; Boomsma, DI; Franco, OH; Bochud, M; Newton-Cheh, C; Munroe, PB; Elliott, P; Chasman, DI; Chakravarti, A; Knight, J; Morris, AP; Levy, D; Tobin, MD; Snieder, H; Caulfield, MJ; Ehret, GB.

In: Hypertension, Vol. 70, No. 3, 2017, p. e4-e19.

Research output: Contribution to journalArticle

Wain, LV, Vaez, A, Jansen, R, Joehanes, R, Van Der Most, PJ, Erzurumluoglu, AM, O'Reilly, PF, Cabrera, CP, Warren, HR, Rose, LM, Verwoert, GC, Hottenga, JJ, Strawbridge, RJ, Esko, T, Arking, DE, Hwang, SJ, Guo, X, Kutalik, Z, Trompet, S, Shrine, N, Teumer, A, Ried, JS, Bis, JC, Smith, AV, Amin, N, Nolte, IM, Lyytikäinen, LP, Mahajan, A, Wareham, NJ, Hofer, E, Joshi, PK, Kristiansson, K, Traglia, M, Havulinna, AS, Goel, A, Nalls, MA, Sõber, S, Vuckovic, D, Luan, J, Del Greco, FM, Ayers, KL, Marrugat, J, Ruggiero, D, Lopez, LM, Niiranen, T, Enroth, S, Jackson, AU, Nelson, CP, Huffman, JE, Zhang, W, Marten, J, Gandin, I, Harris, SE, Zemunik, T, Lu, Y, Evangelou, E, Shah, N, De Borst, MH, Mangino, M, Prins, BP, Campbell, A, Li-Gao, R, Chauhan, G, Oldmeadow, C, Abecasis, G, Abedi, M, Barbieri, CM, Barnes, MR, Batini, C, Beilby, J, Consortium, BIOS, Blake, T, Boehnke, M, Bottinger, EP, Braund, PS, Brown, M, Brumat, M, Campbell, H, Chambers, JC, Cocca, M, Collins, F, Connell, J, Cordell, HJ, Damman, JJ, Davies, G, de Geus, EJ, de Mutsert, R, Deelen, J, Demirkale, Y, Doney, ASF, Dörr, M, Farrall, M, Ferreira, T, Frånberg, M, Gao, H, Giedraitis, V, Gieger, C, Giulianini, F, Gow, AJ, Hamsten, A, Harris, TB, Hofman, A, Holliday, EG, Hui, J, Jarvelin, MR, Johansson, Å, Johnson, AD, Jousilahti, P, Jula, A, Kähönen, M, Kathiresan, S, Khaw, KT, Kolcic, I, Koskinen, S, Langenberg, C, Larson, M, Launer, LJ, Lehne, B, Liewald, DCM, Lin, L, Lind, L, Mach, F, Mamasoula, C, Menni, C, Mifsud, B, Milaneschi, Y, Morgan, A, Morris, AD, Morrison, AC, Munson, PJ, Nandakumar, P, Nguyen, QT, Nutile, T, Oldehinkel, AJ, Oostra, BA, Org, E, Padmanabhan, S, Palotie, A, Paré, G, Pattie, A, Penninx, BWJH, Poulter, N, Pramstaller, PP, Raitakari, OT, Ren, M, Rice, K, Ridker, PM, Riese, H, Ripatti, S, Robino, A, Rotter, JI, Rudan, I, Saba, Y, Saint Pierre, A, Sala, CF, Sarin, AP, Schmidt, R, Scott, R, Seelen, MA, Shields, DC, Siscovick, D, Sorice, R, Stanton, A, Stott, DJ, Sundström, J, Swertz, M, Taylor, KD, Thom, S, Tzoulaki, I, Tzourio, C, Uitterlinden, AG, Völker, U, Vollenweider, P, Wild, S, Willemsen, G, Wright, AF, Yao, J, Thériault, S, Conen, D, Attia, J, Sever, P, Debette, S, Mook-Kanamori, DO, Zeggini, E, Spector, TD, van der Harst, P, Palmer, CNA, Vergnaud, AC, Loos, RJF, Polasek, O, Starr, JM, Girotto, G, Hayward, C, Kooner, JS, Lindgren, CM, Vitart, V, Samani, NJ, Tuomilehto, J, Gyllensten, U, Knekt, P, Deary, IJ, Ciullo, M, Elosua, R, Keavney, BD, Hicks, AA, Scott, RA, Gasparini, P, Laan, M, Liu, Y, Watkins, H, Hartman, CA, Salomaa, V, Toniolo, D, Perola, M, Wilson, JF, Schmidt, H, Zhao, JH, Lehtimäki, T, CM, VD, Gudnason, V, Psaty, BM, Peters, A, Rettig, R, James, A, Jukema, JW, Strachan, DP, Palmas, W, Metspalu, A, Ingelsson, E, Boomsma, DI, Franco, OH, Bochud, M, Newton-Cheh, C, Munroe, PB, Elliott, P, Chasman, DI, Chakravarti, A, Knight, J, Morris, AP, Levy, D, Tobin, MD, Snieder, H, Caulfield, MJ & Ehret, GB 2017, 'Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney', Hypertension, vol. 70, no. 3, pp. e4-e19. https://doi.org/10.1161/HYPERTENSIONAHA.117.09438
Wain, LV ; Vaez, A ; Jansen, R ; Joehanes, R ; Van Der Most, PJ ; Erzurumluoglu, AM ; O'Reilly, PF ; Cabrera, CP ; Warren, HR ; Rose, LM ; Verwoert, GC ; Hottenga, JJ ; Strawbridge, RJ ; Esko, T ; Arking, DE ; Hwang, SJ ; Guo, X ; Kutalik, Z ; Trompet, S ; Shrine, N ; Teumer, A ; Ried, JS ; Bis, JC ; Smith, AV ; Amin, N ; Nolte, IM ; Lyytikäinen, LP ; Mahajan, A ; Wareham, NJ ; Hofer, E ; Joshi, PK ; Kristiansson, K ; Traglia, M ; Havulinna, AS ; Goel, A ; Nalls, MA ; Sõber, S ; Vuckovic, D ; Luan, J ; Del Greco, FM ; Ayers, KL ; Marrugat, J ; Ruggiero, D ; Lopez, LM ; Niiranen, T ; Enroth, S ; Jackson, AU ; Nelson, CP ; Huffman, JE ; Zhang, W ; Marten, J ; Gandin, I ; Harris, SE ; Zemunik, T ; Lu, Y ; Evangelou, E ; Shah, N ; De Borst, MH ; Mangino, M ; Prins, BP ; Campbell, A ; Li-Gao, R ; Chauhan, G ; Oldmeadow, C ; Abecasis, G ; Abedi, M ; Barbieri, CM ; Barnes, MR ; Batini, C ; Beilby, J ; Consortium, BIOS ; Blake, T ; Boehnke, M ; Bottinger, EP ; Braund, PS ; Brown, M ; Brumat, M ; Campbell, H ; Chambers, JC ; Cocca, M ; Collins, F ; Connell, J ; Cordell, HJ ; Damman, JJ ; Davies, G ; de Geus, EJ ; de Mutsert, R ; Deelen, J ; Demirkale, Y ; Doney, ASF ; Dörr, M ; Farrall, M ; Ferreira, T ; Frånberg, M ; Gao, H ; Giedraitis, V ; Gieger, C ; Giulianini, F ; Gow, AJ ; Hamsten, A ; Harris, TB ; Hofman, A ; Holliday, EG ; Hui, J ; Jarvelin, MR ; Johansson, Å ; Johnson, AD ; Jousilahti, P ; Jula, A ; Kähönen, M ; Kathiresan, S ; Khaw, KT ; Kolcic, I ; Koskinen, S ; Langenberg, C ; Larson, M ; Launer, LJ ; Lehne, B ; Liewald, DCM ; Lin, L ; Lind, L ; Mach, F ; Mamasoula, C ; Menni, C ; Mifsud, B ; Milaneschi, Y ; Morgan, A ; Morris, AD ; Morrison, AC ; Munson, PJ ; Nandakumar, P ; Nguyen, QT ; Nutile, T ; Oldehinkel, AJ ; Oostra, BA ; Org, E ; Padmanabhan, S ; Palotie, A ; Paré, G ; Pattie, A ; Penninx, BWJH ; Poulter, N ; Pramstaller, PP ; Raitakari, OT ; Ren, M ; Rice, K ; Ridker, PM ; Riese, H ; Ripatti, S ; Robino, A ; Rotter, JI ; Rudan, I ; Saba, Y ; Saint Pierre, A ; Sala, CF ; Sarin, AP ; Schmidt, R ; Scott, R ; Seelen, MA ; Shields, DC ; Siscovick, D ; Sorice, R ; Stanton, A ; Stott, DJ ; Sundström, J ; Swertz, M ; Taylor, KD ; Thom, S ; Tzoulaki, I ; Tzourio, C ; Uitterlinden, AG ; Völker, U ; Vollenweider, P ; Wild, S ; Willemsen, G ; Wright, AF ; Yao, J ; Thériault, S ; Conen, D ; Attia, J ; Sever, P ; Debette, S ; Mook-Kanamori, DO ; Zeggini, E ; Spector, TD ; van der Harst, P ; Palmer, CNA ; Vergnaud, AC ; Loos, RJF ; Polasek, O ; Starr, JM ; Girotto, G ; Hayward, C ; Kooner, JS ; Lindgren, CM ; Vitart, V ; Samani, NJ ; Tuomilehto, J ; Gyllensten, U ; Knekt, P ; Deary, IJ ; Ciullo, M ; Elosua, R ; Keavney, BD ; Hicks, AA ; Scott, RA ; Gasparini, P ; Laan, M ; Liu, Y ; Watkins, H ; Hartman, CA ; Salomaa, V ; Toniolo, D ; Perola, M ; Wilson, JF ; Schmidt, H ; Zhao, JH ; Lehtimäki, T ; CM, van Duijn ; Gudnason, V ; Psaty, BM ; Peters, A ; Rettig, R ; James, A ; Jukema, JW ; Strachan, DP ; Palmas, W ; Metspalu, A ; Ingelsson, E ; Boomsma, DI ; Franco, OH ; Bochud, M ; Newton-Cheh, C ; Munroe, PB ; Elliott, P ; Chasman, DI ; Chakravarti, A ; Knight, J ; Morris, AP ; Levy, D ; Tobin, MD ; Snieder, H ; Caulfield, MJ ; Ehret, GB. / Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney. In: Hypertension. 2017 ; Vol. 70, No. 3. pp. e4-e19.
@article{dc6d30b82a484a2a8eb9a9e6e0f89f3f,
title = "Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney",
abstract = "Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation. {\circledC} 2017 American Heart Association, Inc.",
author = "LV Wain and A Vaez and R Jansen and R Joehanes and {Van Der Most}, PJ and AM Erzurumluoglu and PF O'Reilly and CP Cabrera and HR Warren and LM Rose and GC Verwoert and JJ Hottenga and RJ Strawbridge and T Esko and DE Arking and SJ Hwang and X Guo and Z Kutalik and S Trompet and N Shrine and A Teumer and JS Ried and JC Bis and AV Smith and N Amin and IM Nolte and LP Lyytik{\"a}inen and A Mahajan and NJ Wareham and E Hofer and PK Joshi and K Kristiansson and M Traglia and AS Havulinna and A Goel and MA Nalls and S S{\~o}ber and D Vuckovic and J Luan and {Del Greco}, FM and KL Ayers and J Marrugat and D Ruggiero and LM Lopez and T Niiranen and S Enroth and AU Jackson and CP Nelson and JE Huffman and W Zhang and J Marten and I Gandin and SE Harris and T Zemunik and Y Lu and E Evangelou and N Shah and {De Borst}, MH and M Mangino and BP Prins and A Campbell and R Li-Gao and G Chauhan and C Oldmeadow and G Abecasis and M Abedi and CM Barbieri and MR Barnes and C Batini and J Beilby and BIOS Consortium and T Blake and M Boehnke and EP Bottinger and PS Braund and M Brown and M Brumat and H Campbell and JC Chambers and M Cocca and F Collins and J Connell and HJ Cordell and JJ Damman and G Davies and {de Geus}, EJ and {de Mutsert}, R and J Deelen and Y Demirkale and ASF Doney and M D{\"o}rr and M Farrall and T Ferreira and M Fr{\aa}nberg and H Gao and V Giedraitis and C Gieger and F Giulianini and AJ Gow and A Hamsten and TB Harris and A Hofman and EG Holliday and J Hui and MR Jarvelin and {\AA} Johansson and AD Johnson and P Jousilahti and A Jula and M K{\"a}h{\"o}nen and S Kathiresan and KT Khaw and I Kolcic and S Koskinen and C Langenberg and M Larson and LJ Launer and B Lehne and DCM Liewald and L Lin and L Lind and F Mach and C Mamasoula and C Menni and B Mifsud and Y Milaneschi and A Morgan and AD Morris and AC Morrison and PJ Munson and P Nandakumar and QT Nguyen and T Nutile and AJ Oldehinkel and BA Oostra and E Org and S Padmanabhan and A Palotie and G Par{\'e} and A Pattie and BWJH Penninx and N Poulter and PP Pramstaller and OT Raitakari and M Ren and K Rice and PM Ridker and H Riese and S Ripatti and A Robino and JI Rotter and I Rudan and Y Saba and {Saint Pierre}, A and CF Sala and AP Sarin and R Schmidt and R Scott and MA Seelen and DC Shields and D Siscovick and R Sorice and A Stanton and DJ Stott and J Sundstr{\"o}m and M Swertz and KD Taylor and S Thom and I Tzoulaki and C Tzourio and AG Uitterlinden and U V{\"o}lker and P Vollenweider and S Wild and G Willemsen and AF Wright and J Yao and S Th{\'e}riault and D Conen and J Attia and P Sever and S Debette and DO Mook-Kanamori and E Zeggini and TD Spector and {van der Harst}, P and CNA Palmer and AC Vergnaud and RJF Loos and O Polasek and JM Starr and G Girotto and C Hayward and JS Kooner and CM Lindgren and V Vitart and NJ Samani and J Tuomilehto and U Gyllensten and P Knekt and IJ Deary and M Ciullo and R Elosua and BD Keavney and AA Hicks and RA Scott and P Gasparini and M Laan and Y Liu and H Watkins and CA Hartman and V Salomaa and D Toniolo and M Perola and JF Wilson and H Schmidt and JH Zhao and T Lehtim{\"a}ki and CM, {van Duijn} and V Gudnason and BM Psaty and A Peters and R Rettig and A James and JW Jukema and DP Strachan and W Palmas and A Metspalu and E Ingelsson and DI Boomsma and OH Franco and M Bochud and C Newton-Cheh and PB Munroe and P Elliott and DI Chasman and A Chakravarti and J Knight and AP Morris and D Levy and MD Tobin and H Snieder and MJ Caulfield and GB Ehret",
year = "2017",
doi = "10.1161/HYPERTENSIONAHA.117.09438",
language = "English",
volume = "70",
pages = "e4--e19",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets from Blood and the Kidney

AU - Wain, LV

AU - Vaez, A

AU - Jansen, R

AU - Joehanes, R

AU - Van Der Most, PJ

AU - Erzurumluoglu, AM

AU - O'Reilly, PF

AU - Cabrera, CP

AU - Warren, HR

AU - Rose, LM

AU - Verwoert, GC

AU - Hottenga, JJ

AU - Strawbridge, RJ

AU - Esko, T

AU - Arking, DE

AU - Hwang, SJ

AU - Guo, X

AU - Kutalik, Z

AU - Trompet, S

AU - Shrine, N

AU - Teumer, A

AU - Ried, JS

AU - Bis, JC

AU - Smith, AV

AU - Amin, N

AU - Nolte, IM

AU - Lyytikäinen, LP

AU - Mahajan, A

AU - Wareham, NJ

AU - Hofer, E

AU - Joshi, PK

AU - Kristiansson, K

AU - Traglia, M

AU - Havulinna, AS

AU - Goel, A

AU - Nalls, MA

AU - Sõber, S

AU - Vuckovic, D

AU - Luan, J

AU - Del Greco, FM

AU - Ayers, KL

AU - Marrugat, J

AU - Ruggiero, D

AU - Lopez, LM

AU - Niiranen, T

AU - Enroth, S

AU - Jackson, AU

AU - Nelson, CP

AU - Huffman, JE

AU - Zhang, W

AU - Marten, J

AU - Gandin, I

AU - Harris, SE

AU - Zemunik, T

AU - Lu, Y

AU - Evangelou, E

AU - Shah, N

AU - De Borst, MH

AU - Mangino, M

AU - Prins, BP

AU - Campbell, A

AU - Li-Gao, R

AU - Chauhan, G

AU - Oldmeadow, C

AU - Abecasis, G

AU - Abedi, M

AU - Barbieri, CM

AU - Barnes, MR

AU - Batini, C

AU - Beilby, J

AU - Consortium, BIOS

AU - Blake, T

AU - Boehnke, M

AU - Bottinger, EP

AU - Braund, PS

AU - Brown, M

AU - Brumat, M

AU - Campbell, H

AU - Chambers, JC

AU - Cocca, M

AU - Collins, F

AU - Connell, J

AU - Cordell, HJ

AU - Damman, JJ

AU - Davies, G

AU - de Geus, EJ

AU - de Mutsert, R

AU - Deelen, J

AU - Demirkale, Y

AU - Doney, ASF

AU - Dörr, M

AU - Farrall, M

AU - Ferreira, T

AU - Frånberg, M

AU - Gao, H

AU - Giedraitis, V

AU - Gieger, C

AU - Giulianini, F

AU - Gow, AJ

AU - Hamsten, A

AU - Harris, TB

AU - Hofman, A

AU - Holliday, EG

AU - Hui, J

AU - Jarvelin, MR

AU - Johansson, Å

AU - Johnson, AD

AU - Jousilahti, P

AU - Jula, A

AU - Kähönen, M

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PY - 2017

Y1 - 2017

N2 - Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation. © 2017 American Heart Association, Inc.

AB - Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation. © 2017 American Heart Association, Inc.

U2 - 10.1161/HYPERTENSIONAHA.117.09438

DO - 10.1161/HYPERTENSIONAHA.117.09438

M3 - Article

VL - 70

SP - e4-e19

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 3

ER -