Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Mary F. Feitosa, Aldi T. Kraja, Daniel I. Chasman, Yun J. Sung, Thomas W. Winkler, Ioanna Ntalla, Xiuqing Guo, Nora Franceschini, Ching Yu Cheng, Xueling Sim, Dina Vojinovic, Jonathan Marten, Solomon K. Musani, Changwei Li, Amy R. Bentley, Michael R. Brown, Karen Schwander, Melissa A. Richard, Raymond Noordam, Hugues Aschard & 252 others Traci M. Bartz, Lawrence F. Bielak, Rajkumar Dorajoo, Virginia Fisher, Fernando P. Hartwig, Andrea R.V.R. Horimoto, Kurt K. Lohman, Alisa K. Manning, Tuomo Rankinen, Albert V. Smith, Salman M. Tajuddin, Mary K. Wojczynski, Maris Alver, Mathilde Boissel, Qiuyin Cai, Archie Campbell, Jin Fang Chai, Xu Chen, Jasmin Divers, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E. Harris, Meian He, Fang Chi Hsu, Anne U. Jackson, Mika Kähönen, Anuradhani Kasturiratne, Pirjo Komulainen, Brigitte Kühnel, Federica Laguzzi, Jian'An Luan, Nana Matoba, Ilja M. Nolte, Sandosh Padmanabhan, Muhammad Riaz, Rico Rueedi, Antonietta Robino, M. Abdullah Said, Robert A. Scott, Tamar Sofer, Alena Stančáková, Fumihiko Takeuchi, Bamidele O. Tayo, Peter J. Van Der Most, Tibor V. Varga, Veronique Vitart, Yajuan Wang, Erin B. Ware, Helen R. Warren, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Najaf Amin, Marzyeh Amini, Dan E. Arking, Tin Aung, Eric Boerwinkle, Ingrid Borecki, Ulrich Broeckel, Morris Brown, Marco Brumat, Gregory L. Burke, Mickaël Canouil, Aravinda Chakravarti, Sabanayagam Charumathi, Yii Der Ida Chen, John M. Connell, Adolfo Correa, Lisa De Las Fuentes, Renée De Mutsert, H. Janaka De Silva, Xuan Deng, Jingzhong Ding, Qing Duan, Charles B. Eaton, Georg Ehret, Ruben N. Eppinga, Evangelos Evangelou, Jessica D. Faul, Stephan B. Felix, Nita G. Forouhi, Terrence Forrester, Oscar H. Franco, Yechiel Friedlander, Ilaria Gandin, He Gao, Mohsen Ghanbari, Bruna Gigante, C. Charles Gu, Dongfeng Gu, Saskia P. Hagenaars, Göran Hallmans, Tamara B. Harris, Jiang He, Sami Heikkinen, Chew Kiat Heng, Makoto Hirata, Barbara V. Howard, M. Arfan Ikram, Ulrich John, Tomohiro Katsuya, Chiea Chuen Khor, Tuomas O. Kilpeläinen, Woon Puay Koh, José E. Krieger, Stephen B. Kritchevsky, Michiaki Kubo, Johanna Kuusisto, Timo A. Lakka, Carl D. Langefeld, Claudia Langenberg, Lenore J. Launer, Benjamin Lehne, Cora E. Lewis, Yize Li, Shiow Lin, Jianjun Liu, Jingmin Liu, Marie Loh, Tin Louie, Reedik Mägi, Colin A. McKenzie, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Lili Milani, Karen L. Mohlke, Yukihide Momozawa, Mike A. Nalls, Christopher P. Nelson, Nona Sotoodehnia, Jill M. Norris, Jeff R. O'Connell, Nicholette D. Palmer, Thomas Perls, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Neil Poulter, Leslie J. Raffel, Olli T. Raitakari, Kathryn Roll, Lynda M. Rose, Frits R. Rosendaal, Jerome I. Rotter, Carsten O. Schmidt, Pamela J. Schreiner, Nicole Schupf, William R. Scott, Peter S. Sever, Yuan Shi, Stephen Sidney, Mario Sims, Colleen M. Sitlani, Jennifer A. Smith, Harold Snieder, John M. Starr, Konstantin Strauch, Heather M. Stringham, Nicholas Y.Q. Tan, Hua Tang, Kent D. Taylor, Yik Ying Teo, Yih Chung Tham, Stephen T. Turner, André G. Uitterlinden, Peter Vollenweider, Melanie Waldenberger, Lihua Wang, Ya Xing Wang, Wen Bin Wei, Christine Williams, Jie Yao, Caizheng Yu, Jian Min Yuan, Wei Zhao, Alan B. Zonderman, Diane M. Becker, Michael Boehnke, Donald W. Bowden, John C. Chambers, Ian J. Deary, Tõnu Esko, Martin Farrall, Paul W. Franks, Barry I. Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Jost Bruno Jonas, Yoichiro Kamatani, Norihiro Kato, Jaspal S. Kooner, Zoltán Kutalik, Markku Laakso, Cathy C. Laurie, Karin Leander, Terho Lehtimäki, Patrik K.E. Magnusson, Albertine J. Oldehinkel, Brenda W.J.H. Penninx, Ozren Polasek, David J. Porteous, Rainer Rauramaa, Nilesh J. Samani, James Scott, Xiao Ou Shu, Pim Van Der Harst, Lynne E. Wagenknecht, Nicholas J. Wareham, Hugh Watkins, David R. Weir, Ananda R. Wickremasinghe, Tangchun Wu, Wei Zheng, Claude Bouchard, Kaare Christensen, Michele K. Evans, Vilmundur Gudnason, Bernardo L. Horta, Sharon L.R. Kardia, Yongmei Liu, Alexandre C. Pereira, Bruce M. Psaty, Paul M. Ridker, Rob M. Van Dam, W. James Gauderman, Xiaofeng Zhu, Dennis O. Mook-Kanamori, Myriam Fornage, Charles N. Rotimi, L. Adrienne Cupples, Tanika N. Kelly, Ervin R. Fox, Caroline Hayward, Cornelia M. Van Duijn, E. Shyong Tai, Tien Yin Wong, Charles Kooperberg, Walter Palmas, Kenneth Rice, Alanna C. Morrison, Paul Elliott, Mark J. Caulfield, Patricia B. Munroe, Dabeeru C. Rao, Michael A. Province, Daniel Levy

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Original languageEnglish
Article numbere0198166
JournalPLoS ONE
Volume13
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Cite this

Feitosa, M. F., Kraja, A. T., Chasman, D. I., Sung, Y. J., Winkler, T. W., Ntalla, I., ... Levy, D. (2018). Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. PLoS ONE, 13(6), [e0198166]. https://doi.org/10.1371/journal.pone.0198166
Feitosa, Mary F. ; Kraja, Aldi T. ; Chasman, Daniel I. ; Sung, Yun J. ; Winkler, Thomas W. ; Ntalla, Ioanna ; Guo, Xiuqing ; Franceschini, Nora ; Cheng, Ching Yu ; Sim, Xueling ; Vojinovic, Dina ; Marten, Jonathan ; Musani, Solomon K. ; Li, Changwei ; Bentley, Amy R. ; Brown, Michael R. ; Schwander, Karen ; Richard, Melissa A. ; Noordam, Raymond ; Aschard, Hugues ; Bartz, Traci M. ; Bielak, Lawrence F. ; Dorajoo, Rajkumar ; Fisher, Virginia ; Hartwig, Fernando P. ; Horimoto, Andrea R.V.R. ; Lohman, Kurt K. ; Manning, Alisa K. ; Rankinen, Tuomo ; Smith, Albert V. ; Tajuddin, Salman M. ; Wojczynski, Mary K. ; Alver, Maris ; Boissel, Mathilde ; Cai, Qiuyin ; Campbell, Archie ; Chai, Jin Fang ; Chen, Xu ; Divers, Jasmin ; Gao, Chuan ; Goel, Anuj ; Hagemeijer, Yanick ; Harris, Sarah E. ; He, Meian ; Hsu, Fang Chi ; Jackson, Anne U. ; Kähönen, Mika ; Kasturiratne, Anuradhani ; Komulainen, Pirjo ; Kühnel, Brigitte ; Laguzzi, Federica ; Luan, Jian'An ; Matoba, Nana ; Nolte, Ilja M. ; Padmanabhan, Sandosh ; Riaz, Muhammad ; Rueedi, Rico ; Robino, Antonietta ; Said, M. Abdullah ; Scott, Robert A. ; Sofer, Tamar ; Stančáková, Alena ; Takeuchi, Fumihiko ; Tayo, Bamidele O. ; Van Der Most, Peter J. ; Varga, Tibor V. ; Vitart, Veronique ; Wang, Yajuan ; Ware, Erin B. ; Warren, Helen R. ; Weiss, Stefan ; Wen, Wanqing ; Yanek, Lisa R. ; Zhang, Weihua ; Zhao, Jing Hua ; Afaq, Saima ; Amin, Najaf ; Amini, Marzyeh ; Arking, Dan E. ; Aung, Tin ; Boerwinkle, Eric ; Borecki, Ingrid ; Broeckel, Ulrich ; Brown, Morris ; Brumat, Marco ; Burke, Gregory L. ; Canouil, Mickaël ; Chakravarti, Aravinda ; Charumathi, Sabanayagam ; Chen, Yii Der Ida ; Connell, John M. ; Correa, Adolfo ; De Las Fuentes, Lisa ; De Mutsert, Renée ; De Silva, H. Janaka ; Deng, Xuan ; Ding, Jingzhong ; Duan, Qing ; Eaton, Charles B. ; Ehret, Georg ; Eppinga, Ruben N. ; Evangelou, Evangelos ; Faul, Jessica D. ; Felix, Stephan B. ; Forouhi, Nita G. ; Forrester, Terrence ; Franco, Oscar H. ; Friedlander, Yechiel ; Gandin, Ilaria ; Gao, He ; Ghanbari, Mohsen ; Gigante, Bruna ; Gu, C. Charles ; Gu, Dongfeng ; Hagenaars, Saskia P. ; Hallmans, Göran ; Harris, Tamara B. ; He, Jiang ; Heikkinen, Sami ; Heng, Chew Kiat ; Hirata, Makoto ; Howard, Barbara V. ; Ikram, M. Arfan ; John, Ulrich ; Katsuya, Tomohiro ; Khor, Chiea Chuen ; Kilpeläinen, Tuomas O. ; Koh, Woon Puay ; Krieger, José E. ; Kritchevsky, Stephen B. ; Kubo, Michiaki ; Kuusisto, Johanna ; Lakka, Timo A. ; Langefeld, Carl D. ; Langenberg, Claudia ; Launer, Lenore J. ; Lehne, Benjamin ; Lewis, Cora E. ; Li, Yize ; Lin, Shiow ; Liu, Jianjun ; Liu, Jingmin ; Loh, Marie ; Louie, Tin ; Mägi, Reedik ; McKenzie, Colin A. ; Meitinger, Thomas ; Metspalu, Andres ; Milaneschi, Yuri ; Milani, Lili ; Mohlke, Karen L. ; Momozawa, Yukihide ; Nalls, Mike A. ; Nelson, Christopher P. ; Sotoodehnia, Nona ; Norris, Jill M. ; O'Connell, Jeff R. ; Palmer, Nicholette D. ; Perls, Thomas ; Pedersen, Nancy L. ; Peters, Annette ; Peyser, Patricia A. ; Poulter, Neil ; Raffel, Leslie J. ; Raitakari, Olli T. ; Roll, Kathryn ; Rose, Lynda M. ; Rosendaal, Frits R. ; Rotter, Jerome I. ; Schmidt, Carsten O. ; Schreiner, Pamela J. ; Schupf, Nicole ; Scott, William R. ; Sever, Peter S. ; Shi, Yuan ; Sidney, Stephen ; Sims, Mario ; Sitlani, Colleen M. ; Smith, Jennifer A. ; Snieder, Harold ; Starr, John M. ; Strauch, Konstantin ; Stringham, Heather M. ; Tan, Nicholas Y.Q. ; Tang, Hua ; Taylor, Kent D. ; Teo, Yik Ying ; Tham, Yih Chung ; Turner, Stephen T. ; Uitterlinden, André G. ; Vollenweider, Peter ; Waldenberger, Melanie ; Wang, Lihua ; Wang, Ya Xing ; Wei, Wen Bin ; Williams, Christine ; Yao, Jie ; Yu, Caizheng ; Yuan, Jian Min ; Zhao, Wei ; Zonderman, Alan B. ; Becker, Diane M. ; Boehnke, Michael ; Bowden, Donald W. ; Chambers, John C. ; Deary, Ian J. ; Esko, Tõnu ; Farrall, Martin ; Franks, Paul W. ; Freedman, Barry I. ; Froguel, Philippe ; Gasparini, Paolo ; Gieger, Christian ; Jonas, Jost Bruno ; Kamatani, Yoichiro ; Kato, Norihiro ; Kooner, Jaspal S. ; Kutalik, Zoltán ; Laakso, Markku ; Laurie, Cathy C. ; Leander, Karin ; Lehtimäki, Terho ; Magnusson, Patrik K.E. ; Oldehinkel, Albertine J. ; Penninx, Brenda W.J.H. ; Polasek, Ozren ; Porteous, David J. ; Rauramaa, Rainer ; Samani, Nilesh J. ; Scott, James ; Shu, Xiao Ou ; Van Der Harst, Pim ; Wagenknecht, Lynne E. ; Wareham, Nicholas J. ; Watkins, Hugh ; Weir, David R. ; Wickremasinghe, Ananda R. ; Wu, Tangchun ; Zheng, Wei ; Bouchard, Claude ; Christensen, Kaare ; Evans, Michele K. ; Gudnason, Vilmundur ; Horta, Bernardo L. ; Kardia, Sharon L.R. ; Liu, Yongmei ; Pereira, Alexandre C. ; Psaty, Bruce M. ; Ridker, Paul M. ; Van Dam, Rob M. ; Gauderman, W. James ; Zhu, Xiaofeng ; Mook-Kanamori, Dennis O. ; Fornage, Myriam ; Rotimi, Charles N. ; Cupples, L. Adrienne ; Kelly, Tanika N. ; Fox, Ervin R. ; Hayward, Caroline ; Van Duijn, Cornelia M. ; Tai, E. Shyong ; Wong, Tien Yin ; Kooperberg, Charles ; Palmas, Walter ; Rice, Kenneth ; Morrison, Alanna C. ; Elliott, Paul ; Caulfield, Mark J. ; Munroe, Patricia B. ; Rao, Dabeeru C. ; Province, Michael A. ; Levy, Daniel. / Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. In: PLoS ONE. 2018 ; Vol. 13, No. 6.
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title = "Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries",
abstract = "Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.",
author = "Feitosa, {Mary F.} and Kraja, {Aldi T.} and Chasman, {Daniel I.} and Sung, {Yun J.} and Winkler, {Thomas W.} and Ioanna Ntalla and Xiuqing Guo and Nora Franceschini and Cheng, {Ching Yu} and Xueling Sim and Dina Vojinovic and Jonathan Marten and Musani, {Solomon K.} and Changwei Li and Bentley, {Amy R.} and Brown, {Michael R.} and Karen Schwander and Richard, {Melissa A.} and Raymond Noordam and Hugues Aschard and Bartz, {Traci M.} and Bielak, {Lawrence F.} and Rajkumar Dorajoo and Virginia Fisher and Hartwig, {Fernando P.} and Horimoto, {Andrea R.V.R.} and Lohman, {Kurt K.} and Manning, {Alisa K.} and Tuomo Rankinen and Smith, {Albert V.} and Tajuddin, {Salman M.} and Wojczynski, {Mary K.} and Maris Alver and Mathilde Boissel and Qiuyin Cai and Archie Campbell and Chai, {Jin Fang} and Xu Chen and Jasmin Divers and Chuan Gao and Anuj Goel and Yanick Hagemeijer and Harris, {Sarah E.} and Meian He and Hsu, {Fang Chi} and Jackson, {Anne U.} and Mika K{\"a}h{\"o}nen and Anuradhani Kasturiratne and Pirjo Komulainen and Brigitte K{\"u}hnel and Federica Laguzzi and Jian'An Luan and Nana Matoba and Nolte, {Ilja M.} and Sandosh Padmanabhan and Muhammad Riaz and Rico Rueedi and Antonietta Robino and Said, {M. Abdullah} and Scott, {Robert A.} and Tamar Sofer and Alena Stanč{\'a}kov{\'a} and Fumihiko Takeuchi and Tayo, {Bamidele O.} and {Van Der Most}, {Peter J.} and Varga, {Tibor V.} and Veronique Vitart and Yajuan Wang and Ware, {Erin B.} and Warren, {Helen R.} and Stefan Weiss and Wanqing Wen and Yanek, {Lisa R.} and Weihua Zhang and Zhao, {Jing Hua} and Saima Afaq and Najaf Amin and Marzyeh Amini and Arking, {Dan E.} and Tin Aung and Eric Boerwinkle and Ingrid Borecki and Ulrich Broeckel and Morris Brown and Marco Brumat and Burke, {Gregory L.} and Micka{\"e}l Canouil and Aravinda Chakravarti and Sabanayagam Charumathi and Chen, {Yii Der Ida} and Connell, {John M.} and Adolfo Correa and {De Las Fuentes}, Lisa and {De Mutsert}, Ren{\'e}e and {De Silva}, {H. Janaka} and Xuan Deng and Jingzhong Ding and Qing Duan and Eaton, {Charles B.} and Georg Ehret and Eppinga, {Ruben N.} and Evangelos Evangelou and Faul, {Jessica D.} and Felix, {Stephan B.} and Forouhi, {Nita G.} and Terrence Forrester and Franco, {Oscar H.} and Yechiel Friedlander and Ilaria Gandin and He Gao and Mohsen Ghanbari and Bruna Gigante and Gu, {C. Charles} and Dongfeng Gu and Hagenaars, {Saskia P.} and G{\"o}ran Hallmans and Harris, {Tamara B.} and Jiang He and Sami Heikkinen and Heng, {Chew Kiat} and Makoto Hirata and Howard, {Barbara V.} and Ikram, {M. Arfan} and Ulrich John and Tomohiro Katsuya and Khor, {Chiea Chuen} and Kilpel{\"a}inen, {Tuomas O.} and Koh, {Woon Puay} and Krieger, {Jos{\'e} E.} and Kritchevsky, {Stephen B.} and Michiaki Kubo and Johanna Kuusisto and Lakka, {Timo A.} and Langefeld, {Carl D.} and Claudia Langenberg and Launer, {Lenore J.} and Benjamin Lehne and Lewis, {Cora E.} and Yize Li and Shiow Lin and Jianjun Liu and Jingmin Liu and Marie Loh and Tin Louie and Reedik M{\"a}gi and McKenzie, {Colin A.} and Thomas Meitinger and Andres Metspalu and Yuri Milaneschi and Lili Milani and Mohlke, {Karen L.} and Yukihide Momozawa and Nalls, {Mike A.} and Nelson, {Christopher P.} and Nona Sotoodehnia and Norris, {Jill M.} and O'Connell, {Jeff R.} and Palmer, {Nicholette D.} and Thomas Perls and Pedersen, {Nancy L.} and Annette Peters and Peyser, {Patricia A.} and Neil Poulter and Raffel, {Leslie J.} and Raitakari, {Olli T.} and Kathryn Roll and Rose, {Lynda M.} and Rosendaal, {Frits R.} and Rotter, {Jerome I.} and Schmidt, {Carsten O.} and Schreiner, {Pamela J.} and Nicole Schupf and Scott, {William R.} and Sever, {Peter S.} and Yuan Shi and Stephen Sidney and Mario Sims and Sitlani, {Colleen M.} and Smith, {Jennifer A.} and Harold Snieder and Starr, {John M.} and Konstantin Strauch and Stringham, {Heather M.} and Tan, {Nicholas Y.Q.} and Hua Tang and Taylor, {Kent D.} and Teo, {Yik Ying} and Tham, {Yih Chung} and Turner, {Stephen T.} and Uitterlinden, {Andr{\'e} G.} and Peter Vollenweider and Melanie Waldenberger and Lihua Wang and Wang, {Ya Xing} and Wei, {Wen Bin} and Christine Williams and Jie Yao and Caizheng Yu and Yuan, {Jian Min} and Wei Zhao and Zonderman, {Alan B.} and Becker, {Diane M.} and Michael Boehnke and Bowden, {Donald W.} and Chambers, {John C.} and Deary, {Ian J.} and T{\~o}nu Esko and Martin Farrall and Franks, {Paul W.} and Freedman, {Barry I.} and Philippe Froguel and Paolo Gasparini and Christian Gieger and Jonas, {Jost Bruno} and Yoichiro Kamatani and Norihiro Kato and Kooner, {Jaspal S.} and Zolt{\'a}n Kutalik and Markku Laakso and Laurie, {Cathy C.} and Karin Leander and Terho Lehtim{\"a}ki and Magnusson, {Patrik K.E.} and Oldehinkel, {Albertine J.} and Penninx, {Brenda W.J.H.} and Ozren Polasek and Porteous, {David J.} and Rainer Rauramaa and Samani, {Nilesh J.} and James Scott and Shu, {Xiao Ou} and {Van Der Harst}, Pim and Wagenknecht, {Lynne E.} and Wareham, {Nicholas J.} and Hugh Watkins and Weir, {David R.} and Wickremasinghe, {Ananda R.} and Tangchun Wu and Wei Zheng and Claude Bouchard and Kaare Christensen and Evans, {Michele K.} and Vilmundur Gudnason and Horta, {Bernardo L.} and Kardia, {Sharon L.R.} and Yongmei Liu and Pereira, {Alexandre C.} and Psaty, {Bruce M.} and Ridker, {Paul M.} and {Van Dam}, {Rob M.} and Gauderman, {W. James} and Xiaofeng Zhu and Mook-Kanamori, {Dennis O.} and Myriam Fornage and Rotimi, {Charles N.} and Cupples, {L. Adrienne} and Kelly, {Tanika N.} and Fox, {Ervin R.} and Caroline Hayward and {Van Duijn}, {Cornelia M.} and Tai, {E. Shyong} and Wong, {Tien Yin} and Charles Kooperberg and Walter Palmas and Kenneth Rice and Morrison, {Alanna C.} and Paul Elliott and Caulfield, {Mark J.} and Munroe, {Patricia B.} and Rao, {Dabeeru C.} and Province, {Michael A.} and Daniel Levy",
year = "2018",
month = "6",
day = "1",
doi = "10.1371/journal.pone.0198166",
language = "English",
volume = "13",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, X, Franceschini, N, Cheng, CY, Sim, X, Vojinovic, D, Marten, J, Musani, SK, Li, C, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, ARVR, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, SM, Wojczynski, MK, Alver, M, Boissel, M, Cai, Q, Campbell, A, Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, M, Hsu, FC, Jackson, AU, Kähönen, M, Kasturiratne, A, Komulainen, P, Kühnel, B, Laguzzi, F, Luan, JA, Matoba, N, Nolte, IM, Padmanabhan, S, Riaz, M, Rueedi, R, Robino, A, Said, MA, Scott, RA, Sofer, T, Stančáková, A, Takeuchi, F, Tayo, BO, Van Der Most, PJ, Varga, TV, Vitart, V, Wang, Y, Ware, EB, Warren, HR, Weiss, S, Wen, W, Yanek, LR, Zhang, W, Zhao, JH, Afaq, S, Amin, N, Amini, M, Arking, DE, Aung, T, Boerwinkle, E, Borecki, I, Broeckel, U, Brown, M, Brumat, M, Burke, GL, Canouil, M, Chakravarti, A, Charumathi, S, Chen, YDI, Connell, JM, Correa, A, De Las Fuentes, L, De Mutsert, R, De Silva, HJ, Deng, X, Ding, J, Duan, Q, Eaton, CB, Ehret, G, Eppinga, RN, Evangelou, E, Faul, JD, Felix, SB, Forouhi, NG, Forrester, T, Franco, OH, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, M, Gigante, B, Gu, CC, Gu, D, Hagenaars, SP, Hallmans, G, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hirata, M, Howard, BV, Ikram, MA, John, U, Katsuya, T, Khor, CC, Kilpeläinen, TO, Koh, WP, Krieger, JE, Kritchevsky, SB, Kubo, M, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lehne, B, Lewis, CE, Li, Y, Lin, S, Liu, J, Liu, J, Loh, M, Louie, T, Mägi, R, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, KL, Momozawa, Y, Nalls, MA, Nelson, CP, Sotoodehnia, N, Norris, JM, O'Connell, JR, Palmer, ND, Perls, T, Pedersen, NL, Peters, A, Peyser, PA, Poulter, N, Raffel, LJ, Raitakari, OT, Roll, K, Rose, LM, Rosendaal, FR, Rotter, JI, Schmidt, CO, Schreiner, PJ, Schupf, N, Scott, WR, Sever, PS, Shi, Y, Sidney, S, Sims, M, Sitlani, CM, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Stringham, HM, Tan, NYQ, Tang, H, Taylor, KD, Teo, YY, Tham, YC, Turner, ST, Uitterlinden, AG, Vollenweider, P, Waldenberger, M, Wang, L, Wang, YX, Wei, WB, Williams, C, Yao, J, Yu, C, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Deary, IJ, Esko, T, Farrall, M, Franks, PW, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Jonas, JB, Kamatani, Y, Kato, N, Kooner, JS, Kutalik, Z, Laakso, M, Laurie, CC, Leander, K, Lehtimäki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, BWJH, Polasek, O, Porteous, DJ, Rauramaa, R, Samani, NJ, Scott, J, Shu, XO, Van Der Harst, P, Wagenknecht, LE, Wareham, NJ, Watkins, H, Weir, DR, Wickremasinghe, AR, Wu, T, Zheng, W, Bouchard, C, Christensen, K, Evans, MK, Gudnason, V, Horta, BL, Kardia, SLR, Liu, Y, Pereira, AC, Psaty, BM, Ridker, PM, Van Dam, RM, Gauderman, WJ, Zhu, X, Mook-Kanamori, DO, Fornage, M, Rotimi, CN, Cupples, LA, Kelly, TN, Fox, ER, Hayward, C, Van Duijn, CM, Tai, ES, Wong, TY, Kooperberg, C, Palmas, W, Rice, K, Morrison, AC, Elliott, P, Caulfield, MJ, Munroe, PB, Rao, DC, Province, MA & Levy, D 2018, 'Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries' PLoS ONE, vol. 13, no. 6, e0198166. https://doi.org/10.1371/journal.pone.0198166

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. / Feitosa, Mary F.; Kraja, Aldi T.; Chasman, Daniel I.; Sung, Yun J.; Winkler, Thomas W.; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Cheng, Ching Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K.; Li, Changwei; Bentley, Amy R.; Brown, Michael R.; Schwander, Karen; Richard, Melissa A.; Noordam, Raymond; Aschard, Hugues; Bartz, Traci M.; Bielak, Lawrence F.; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P.; Horimoto, Andrea R.V.R.; Lohman, Kurt K.; Manning, Alisa K.; Rankinen, Tuomo; Smith, Albert V.; Tajuddin, Salman M.; Wojczynski, Mary K.; Alver, Maris; Boissel, Mathilde; Cai, Qiuyin; Campbell, Archie; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gao, Chuan; Goel, Anuj; Hagemeijer, Yanick; Harris, Sarah E.; He, Meian; Hsu, Fang Chi; Jackson, Anne U.; Kähönen, Mika; Kasturiratne, Anuradhani; Komulainen, Pirjo; Kühnel, Brigitte; Laguzzi, Federica; Luan, Jian'An; Matoba, Nana; Nolte, Ilja M.; Padmanabhan, Sandosh; Riaz, Muhammad; Rueedi, Rico; Robino, Antonietta; Said, M. Abdullah; Scott, Robert A.; Sofer, Tamar; Stančáková, Alena; Takeuchi, Fumihiko; Tayo, Bamidele O.; Van Der Most, Peter J.; Varga, Tibor V.; Vitart, Veronique; Wang, Yajuan; Ware, Erin B.; Warren, Helen R.; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R.; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Amin, Najaf; Amini, Marzyeh; Arking, Dan E.; Aung, Tin; Boerwinkle, Eric; Borecki, Ingrid; Broeckel, Ulrich; Brown, Morris; Brumat, Marco; Burke, Gregory L.; Canouil, Mickaël; Chakravarti, Aravinda; Charumathi, Sabanayagam; Chen, Yii Der Ida; Connell, John M.; Correa, Adolfo; De Las Fuentes, Lisa; De Mutsert, Renée; De Silva, H. Janaka; Deng, Xuan; Ding, Jingzhong; Duan, Qing; Eaton, Charles B.; Ehret, Georg; Eppinga, Ruben N.; Evangelou, Evangelos; Faul, Jessica D.; Felix, Stephan B.; Forouhi, Nita G.; Forrester, Terrence; Franco, Oscar H.; Friedlander, Yechiel; Gandin, Ilaria; Gao, He; Ghanbari, Mohsen; Gigante, Bruna; Gu, C. Charles; Gu, Dongfeng; Hagenaars, Saskia P.; Hallmans, Göran; Harris, Tamara B.; He, Jiang; Heikkinen, Sami; Heng, Chew Kiat; Hirata, Makoto; Howard, Barbara V.; Ikram, M. Arfan; John, Ulrich; Katsuya, Tomohiro; Khor, Chiea Chuen; Kilpeläinen, Tuomas O.; Koh, Woon Puay; Krieger, José E.; Kritchevsky, Stephen B.; Kubo, Michiaki; Kuusisto, Johanna; Lakka, Timo A.; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lehne, Benjamin; Lewis, Cora E.; Li, Yize; Lin, Shiow; Liu, Jianjun; Liu, Jingmin; Loh, Marie; Louie, Tin; Mägi, Reedik; McKenzie, Colin A.; Meitinger, Thomas; Metspalu, Andres; Milaneschi, Yuri; Milani, Lili; Mohlke, Karen L.; Momozawa, Yukihide; Nalls, Mike A.; Nelson, Christopher P.; Sotoodehnia, Nona; Norris, Jill M.; O'Connell, Jeff R.; Palmer, Nicholette D.; Perls, Thomas; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Poulter, Neil; Raffel, Leslie J.; Raitakari, Olli T.; Roll, Kathryn; Rose, Lynda M.; Rosendaal, Frits R.; Rotter, Jerome I.; Schmidt, Carsten O.; Schreiner, Pamela J.; Schupf, Nicole; Scott, William R.; Sever, Peter S.; Shi, Yuan; Sidney, Stephen; Sims, Mario; Sitlani, Colleen M.; Smith, Jennifer A.; Snieder, Harold; Starr, John M.; Strauch, Konstantin; Stringham, Heather M.; Tan, Nicholas Y.Q.; Tang, Hua; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Turner, Stephen T.; Uitterlinden, André G.; Vollenweider, Peter; Waldenberger, Melanie; Wang, Lihua; Wang, Ya Xing; Wei, Wen Bin; Williams, Christine; Yao, Jie; Yu, Caizheng; Yuan, Jian Min; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; Chambers, John C.; Deary, Ian J.; Esko, Tõnu; Farrall, Martin; Franks, Paul W.; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Jonas, Jost Bruno; Kamatani, Yoichiro; Kato, Norihiro; Kooner, Jaspal S.; Kutalik, Zoltán; Laakso, Markku; Laurie, Cathy C.; Leander, Karin; Lehtimäki, Terho; Magnusson, Patrik K.E.; Oldehinkel, Albertine J.; Penninx, Brenda W.J.H.; Polasek, Ozren; Porteous, David J.; Rauramaa, Rainer; Samani, Nilesh J.; Scott, James; Shu, Xiao Ou; Van Der Harst, Pim; Wagenknecht, Lynne E.; Wareham, Nicholas J.; Watkins, Hugh; Weir, David R.; Wickremasinghe, Ananda R.; Wu, Tangchun; Zheng, Wei; Bouchard, Claude; Christensen, Kaare; Evans, Michele K.; Gudnason, Vilmundur; Horta, Bernardo L.; Kardia, Sharon L.R.; Liu, Yongmei; Pereira, Alexandre C.; Psaty, Bruce M.; Ridker, Paul M.; Van Dam, Rob M.; Gauderman, W. James; Zhu, Xiaofeng; Mook-Kanamori, Dennis O.; Fornage, Myriam; Rotimi, Charles N.; Cupples, L. Adrienne; Kelly, Tanika N.; Fox, Ervin R.; Hayward, Caroline; Van Duijn, Cornelia M.; Tai, E. Shyong; Wong, Tien Yin; Kooperberg, Charles; Palmas, Walter; Rice, Kenneth; Morrison, Alanna C.; Elliott, Paul; Caulfield, Mark J.; Munroe, Patricia B.; Rao, Dabeeru C.; Province, Michael A.; Levy, Daniel.

In: PLoS ONE, Vol. 13, No. 6, e0198166, 01.06.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

AU - Feitosa, Mary F.

AU - Kraja, Aldi T.

AU - Chasman, Daniel I.

AU - Sung, Yun J.

AU - Winkler, Thomas W.

AU - Ntalla, Ioanna

AU - Guo, Xiuqing

AU - Franceschini, Nora

AU - Cheng, Ching Yu

AU - Sim, Xueling

AU - Vojinovic, Dina

AU - Marten, Jonathan

AU - Musani, Solomon K.

AU - Li, Changwei

AU - Bentley, Amy R.

AU - Brown, Michael R.

AU - Schwander, Karen

AU - Richard, Melissa A.

AU - Noordam, Raymond

AU - Aschard, Hugues

AU - Bartz, Traci M.

AU - Bielak, Lawrence F.

AU - Dorajoo, Rajkumar

AU - Fisher, Virginia

AU - Hartwig, Fernando P.

AU - Horimoto, Andrea R.V.R.

AU - Lohman, Kurt K.

AU - Manning, Alisa K.

AU - Rankinen, Tuomo

AU - Smith, Albert V.

AU - Tajuddin, Salman M.

AU - Wojczynski, Mary K.

AU - Alver, Maris

AU - Boissel, Mathilde

AU - Cai, Qiuyin

AU - Campbell, Archie

AU - Chai, Jin Fang

AU - Chen, Xu

AU - Divers, Jasmin

AU - Gao, Chuan

AU - Goel, Anuj

AU - Hagemeijer, Yanick

AU - Harris, Sarah E.

AU - He, Meian

AU - Hsu, Fang Chi

AU - Jackson, Anne U.

AU - Kähönen, Mika

AU - Kasturiratne, Anuradhani

AU - Komulainen, Pirjo

AU - Kühnel, Brigitte

AU - Laguzzi, Federica

AU - Luan, Jian'An

AU - Matoba, Nana

AU - Nolte, Ilja M.

AU - Padmanabhan, Sandosh

AU - Riaz, Muhammad

AU - Rueedi, Rico

AU - Robino, Antonietta

AU - Said, M. Abdullah

AU - Scott, Robert A.

AU - Sofer, Tamar

AU - Stančáková, Alena

AU - Takeuchi, Fumihiko

AU - Tayo, Bamidele O.

AU - Van Der Most, Peter J.

AU - Varga, Tibor V.

AU - Vitart, Veronique

AU - Wang, Yajuan

AU - Ware, Erin B.

AU - Warren, Helen R.

AU - Weiss, Stefan

AU - Wen, Wanqing

AU - Yanek, Lisa R.

AU - Zhang, Weihua

AU - Zhao, Jing Hua

AU - Afaq, Saima

AU - Amin, Najaf

AU - Amini, Marzyeh

AU - Arking, Dan E.

AU - Aung, Tin

AU - Boerwinkle, Eric

AU - Borecki, Ingrid

AU - Broeckel, Ulrich

AU - Brown, Morris

AU - Brumat, Marco

AU - Burke, Gregory L.

AU - Canouil, Mickaël

AU - Chakravarti, Aravinda

AU - Charumathi, Sabanayagam

AU - Chen, Yii Der Ida

AU - Connell, John M.

AU - Correa, Adolfo

AU - De Las Fuentes, Lisa

AU - De Mutsert, Renée

AU - De Silva, H. Janaka

AU - Deng, Xuan

AU - Ding, Jingzhong

AU - Duan, Qing

AU - Eaton, Charles B.

AU - Ehret, Georg

AU - Eppinga, Ruben N.

AU - Evangelou, Evangelos

AU - Faul, Jessica D.

AU - Felix, Stephan B.

AU - Forouhi, Nita G.

AU - Forrester, Terrence

AU - Franco, Oscar H.

AU - Friedlander, Yechiel

AU - Gandin, Ilaria

AU - Gao, He

AU - Ghanbari, Mohsen

AU - Gigante, Bruna

AU - Gu, C. Charles

AU - Gu, Dongfeng

AU - Hagenaars, Saskia P.

AU - Hallmans, Göran

AU - Harris, Tamara B.

AU - He, Jiang

AU - Heikkinen, Sami

AU - Heng, Chew Kiat

AU - Hirata, Makoto

AU - Howard, Barbara V.

AU - Ikram, M. Arfan

AU - John, Ulrich

AU - Katsuya, Tomohiro

AU - Khor, Chiea Chuen

AU - Kilpeläinen, Tuomas O.

AU - Koh, Woon Puay

AU - Krieger, José E.

AU - Kritchevsky, Stephen B.

AU - Kubo, Michiaki

AU - Kuusisto, Johanna

AU - Lakka, Timo A.

AU - Langefeld, Carl D.

AU - Langenberg, Claudia

AU - Launer, Lenore J.

AU - Lehne, Benjamin

AU - Lewis, Cora E.

AU - Li, Yize

AU - Lin, Shiow

AU - Liu, Jianjun

AU - Liu, Jingmin

AU - Loh, Marie

AU - Louie, Tin

AU - Mägi, Reedik

AU - McKenzie, Colin A.

AU - Meitinger, Thomas

AU - Metspalu, Andres

AU - Milaneschi, Yuri

AU - Milani, Lili

AU - Mohlke, Karen L.

AU - Momozawa, Yukihide

AU - Nalls, Mike A.

AU - Nelson, Christopher P.

AU - Sotoodehnia, Nona

AU - Norris, Jill M.

AU - O'Connell, Jeff R.

AU - Palmer, Nicholette D.

AU - Perls, Thomas

AU - Pedersen, Nancy L.

AU - Peters, Annette

AU - Peyser, Patricia A.

AU - Poulter, Neil

AU - Raffel, Leslie J.

AU - Raitakari, Olli T.

AU - Roll, Kathryn

AU - Rose, Lynda M.

AU - Rosendaal, Frits R.

AU - Rotter, Jerome I.

AU - Schmidt, Carsten O.

AU - Schreiner, Pamela J.

AU - Schupf, Nicole

AU - Scott, William R.

AU - Sever, Peter S.

AU - Shi, Yuan

AU - Sidney, Stephen

AU - Sims, Mario

AU - Sitlani, Colleen M.

AU - Smith, Jennifer A.

AU - Snieder, Harold

AU - Starr, John M.

AU - Strauch, Konstantin

AU - Stringham, Heather M.

AU - Tan, Nicholas Y.Q.

AU - Tang, Hua

AU - Taylor, Kent D.

AU - Teo, Yik Ying

AU - Tham, Yih Chung

AU - Turner, Stephen T.

AU - Uitterlinden, André G.

AU - Vollenweider, Peter

AU - Waldenberger, Melanie

AU - Wang, Lihua

AU - Wang, Ya Xing

AU - Wei, Wen Bin

AU - Williams, Christine

AU - Yao, Jie

AU - Yu, Caizheng

AU - Yuan, Jian Min

AU - Zhao, Wei

AU - Zonderman, Alan B.

AU - Becker, Diane M.

AU - Boehnke, Michael

AU - Bowden, Donald W.

AU - Chambers, John C.

AU - Deary, Ian J.

AU - Esko, Tõnu

AU - Farrall, Martin

AU - Franks, Paul W.

AU - Freedman, Barry I.

AU - Froguel, Philippe

AU - Gasparini, Paolo

AU - Gieger, Christian

AU - Jonas, Jost Bruno

AU - Kamatani, Yoichiro

AU - Kato, Norihiro

AU - Kooner, Jaspal S.

AU - Kutalik, Zoltán

AU - Laakso, Markku

AU - Laurie, Cathy C.

AU - Leander, Karin

AU - Lehtimäki, Terho

AU - Magnusson, Patrik K.E.

AU - Oldehinkel, Albertine J.

AU - Penninx, Brenda W.J.H.

AU - Polasek, Ozren

AU - Porteous, David J.

AU - Rauramaa, Rainer

AU - Samani, Nilesh J.

AU - Scott, James

AU - Shu, Xiao Ou

AU - Van Der Harst, Pim

AU - Wagenknecht, Lynne E.

AU - Wareham, Nicholas J.

AU - Watkins, Hugh

AU - Weir, David R.

AU - Wickremasinghe, Ananda R.

AU - Wu, Tangchun

AU - Zheng, Wei

AU - Bouchard, Claude

AU - Christensen, Kaare

AU - Evans, Michele K.

AU - Gudnason, Vilmundur

AU - Horta, Bernardo L.

AU - Kardia, Sharon L.R.

AU - Liu, Yongmei

AU - Pereira, Alexandre C.

AU - Psaty, Bruce M.

AU - Ridker, Paul M.

AU - Van Dam, Rob M.

AU - Gauderman, W. James

AU - Zhu, Xiaofeng

AU - Mook-Kanamori, Dennis O.

AU - Fornage, Myriam

AU - Rotimi, Charles N.

AU - Cupples, L. Adrienne

AU - Kelly, Tanika N.

AU - Fox, Ervin R.

AU - Hayward, Caroline

AU - Van Duijn, Cornelia M.

AU - Tai, E. Shyong

AU - Wong, Tien Yin

AU - Kooperberg, Charles

AU - Palmas, Walter

AU - Rice, Kenneth

AU - Morrison, Alanna C.

AU - Elliott, Paul

AU - Caulfield, Mark J.

AU - Munroe, Patricia B.

AU - Rao, Dabeeru C.

AU - Province, Michael A.

AU - Levy, Daniel

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

AB - Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

UR - http://www.scopus.com/inward/record.url?scp=85049155160&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0198166

DO - 10.1371/journal.pone.0198166

M3 - Article

VL - 13

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 6

M1 - e0198166

ER -