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

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 a... Full description

Journal Title: Feitosa M. F., A. T. Kraja, D. I. Chasman, Y. J. Sung, T. W. Winkler, I. Ntalla, X. Guo, et al. 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. doi:10.1371/journal.pone.0198166. http://dx.doi.org/10.1371/journal.pone.0198166.
Main Author: Feitosa, Mary F.
Other Authors: 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 , Ida Chen, Yii-Der , 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 , Study, Lifelines Cohort , 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.
Format: Electronic Article Electronic Article
Language: English
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ID: DOI: 10.1371/journal.pone.0198166
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title: Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
format: Article
creator:
  • 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
  • Ida Chen, Yii-Der
  • 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
  • Study, Lifelines Cohort
  • 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.
subjects:
  • Biology And Life Sciences
  • Nutrition
  • Diet
  • Alcohol Consumption
  • Medicine And Health Sciences
  • Mathematical And Statistical Techniques
  • Statistical Methods
  • Meta-Analysis
  • Physical Sciences
  • Mathematics
  • Statistics (Mathematics)
  • Computational Biology
  • Genome Complexity
  • Introns
  • Genetics
  • Genomics
  • Vascular Medicine
  • Blood Pressure
  • Genetic Loci
  • Molecular Biology
  • Molecular Biology Techniques
  • Gene Mapping
  • Alleles
  • Psychology
  • Addiction
  • Alcoholism
  • Social Sciences
  • Mental Health And Psychiatry
  • Substance-Related Disorders
  • Public And Occupational Health
ispartof: Feitosa, M. F., A. T. Kraja, D. I. Chasman, Y. J. Sung, T. W. Winkler, I. Ntalla, X. Guo, et al. 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. doi:10.1371/journal.pone.0198166. http://dx.doi.org/10.1371/journal.pone.0198166.
description: 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 x 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 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 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.
language: eng
source:
identifier: DOI: 10.1371/journal.pone.0198166
fulltext: fulltext_linktorsrc
url: Link


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titleNovel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
creatorFeitosa, 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 ; Ida Chen, Yii-Der ; 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 ; Study, Lifelines Cohort ; 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.
ispartofFeitosa, M. F., A. T. Kraja, D. I. Chasman, Y. J. Sung, T. W. Winkler, I. Ntalla, X. Guo, et al. 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. doi:10.1371/journal.pone.0198166. http://dx.doi.org/10.1371/journal.pone.0198166.
identifierDOI: 10.1371/journal.pone.0198166
subjectBiology And Life Sciences ; Nutrition ; Diet ; Alcohol Consumption ; Medicine And Health Sciences ; Mathematical And Statistical Techniques ; Statistical Methods ; Meta-Analysis ; Physical Sciences ; Mathematics ; Statistics (Mathematics) ; Computational Biology ; Genome Complexity ; Introns ; Genetics ; Genomics ; Vascular Medicine ; Blood Pressure ; Genetic Loci ; Molecular Biology ; Molecular Biology Techniques ; Gene Mapping ; Alleles ; Psychology ; Addiction ; Alcoholism ; Social Sciences ; Mental Health And Psychiatry ; Substance-Related Disorders ; Public And Occupational Health
descriptionHeavy 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 x 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 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 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.
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0Feitosa, Mary F.
1Kraja, Aldi T.
2Chasman, Daniel I.
3Sung, Yun J.
4Winkler, Thomas W.
5Ntalla, Ioanna
6Guo, Xiuqing
7Franceschini, Nora
8Cheng, Ching-Yu
9Sim, Xueling
10Vojinovic, Dina
11Marten, Jonathan
12Musani, Solomon K.
13Li, Changwei
14Bentley, Amy R.
15Brown, Michael R.
16Schwander, Karen
17Richard, Melissa A.
18Noordam, Raymond
19Aschard, Hugues
20Bartz, Traci M.
21Bielak, Lawrence F.
22Dorajoo, Rajkumar
23Fisher, Virginia
24Hartwig, Fernando P.
25Horimoto, Andrea R. V. R.
26Lohman, Kurt K.
27Manning, Alisa K.
28Rankinen, Tuomo
29Smith, Albert V.
30Tajuddin, Salman M.
31Wojczynski, Mary K.
32Alver, Maris
33Boissel, Mathilde
34Cai, Qiuyin
35Campbell, Archie
36Chai, Jin Fang
37Chen, Xu
38Divers, Jasmin
39Gao, Chuan
40Goel, Anuj
41Hagemeijer, Yanick
42Harris, Sarah E.
43He, Meian
44Hsu, Fang-Chi
45Jackson, Anne U.
46Kähönen, Mika
47Kasturiratne, Anuradhani
48Komulainen, Pirjo
49Kühnel, Brigitte
50Laguzzi, Federica
51Luan, Jian'an
52Matoba, Nana
53Nolte, Ilja M.
54Padmanabhan, Sandosh
55Riaz, Muhammad
56Rueedi, Rico
57Robino, Antonietta
58Said, M. Abdullah
59Scott, Robert A.
60Sofer, Tamar
61Stančáková, Alena
62Takeuchi, Fumihiko
63Tayo, Bamidele O.
64van der Most, Peter J.
65Varga, Tibor V.
66Vitart, Veronique
67Wang, Yajuan
68Ware, Erin B.
69Warren, Helen R.
70Weiss, Stefan
71Wen, Wanqing
72Yanek, Lisa R.
73Zhang, Weihua
74Zhao, Jing Hua
75Afaq, Saima
76Amin, Najaf
77Amini, Marzyeh
78Arking, Dan E.
79Aung, Tin
80Boerwinkle, Eric
81Borecki, Ingrid
82Broeckel, Ulrich
83Brown, Morris
84Brumat, Marco
85Burke, Gregory L.
86Canouil, Mickaël
87Chakravarti, Aravinda
88Charumathi, Sabanayagam
89Ida Chen, Yii-Der
90Connell, John M.
91Correa, Adolfo
92de las Fuentes, Lisa
93de Mutsert, Renée
94de Silva, H. Janaka
95Deng, Xuan
96Ding, Jingzhong
97Duan, Qing
98Eaton, Charles B.
99Ehret, Georg
100...
titleNovel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
descriptionHeavy 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 x 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 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 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.
subject
0Biology and Life Sciences
1Nutrition
2Diet
3Alcohol Consumption
4Medicine and Health Sciences
5Mathematical and Statistical Techniques
6Statistical Methods
7Meta-Analysis
8Physical Sciences
9Mathematics
10Statistics (Mathematics)
11Computational Biology
12Genome Complexity
13Introns
14Genetics
15Genomics
16Vascular Medicine
17Blood Pressure
18Genetic Loci
19Molecular Biology
20Molecular Biology Techniques
21Gene Mapping
22Alleles
23Psychology
24Addiction
25Alcoholism
26Social Sciences
27Mental Health and Psychiatry
28Substance-Related Disorders
29Public and Occupational Health
general
0Digital Access to Scholarship at Harvard (DASH)
1Public Library of Science
2English
310.1371/journal.pone.0198166
sourceiddash
recordiddash1/37298442
rsrctypearticle
creationdate2018
searchscopedash
scopedash
lsr30VSR-Enriched:[issue, orcidid, vol, issn, pages, pqid, galeid, eissn]
sort
titleNovel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
authorFeitosa, 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 ; Ida Chen, Yii-Der ; 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 ; Study, Lifelines Cohort ; 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.
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newrecords20180731
languageeng
creationdate2018
topic
0Biology And Life Sciences
1Nutrition
2Diet
3Alcohol Consumption
4Medicine And Health Sciences
5Mathematical And Statistical Techniques
6Statistical Methods
7Meta-Analysis
8Physical Sciences
9Mathematics
10Statistics (Mathematics)
11Computational Biology
12Genome Complexity
13Introns
14Genetics
15Genomics
16Vascular Medicine
17Blood Pressure
18Genetic Loci
19Molecular Biology
20Molecular Biology Techniques
21Gene Mapping
22Alleles
23Psychology
24Addiction
25Alcoholism
26Social Sciences
27Mental Health And Psychiatry
28Substance-Related Disorders
29Public And Occupational Health
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rsrctypearticles
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0Feitosa, Mary F
1Kraja, Aldi T
2Chasman, Daniel I
3Sung, Yun J
4Winkler, Thomas W
5Ntalla, Ioanna
6Guo, Xiuqing
7Franceschini, Nora
8Cheng, Ching-Yu
9Sim, Xueling
10Vojinovic, Dina
11Marten, Jonathan
12Musani, Solomon K
13Li, Changwei
14Bentley, Amy R
15Brown, Michael R
16Schwander, Karen
17Richard, Melissa A
18Noordam, Raymond
19Aschard, Hugues
20Bartz, Traci M
21Bielak, Lawrence F
22Dorajoo, Rajkumar
23Fisher, Virginia
24Hartwig, Fernando P
25Horimoto, Andrea R. V. R
26Lohman, Kurt K
27Manning, Alisa K
28Rankinen, Tuomo
29Smith, Albert V
30Tajuddin, Salman M
31Wojczynski, Mary K
32Alver, Maris
33Boissel, Mathilde
34Cai, Qiuyin
35Campbell, Archie
36Chai, Jin Fang
37Chen, Xu
38Divers, Jasmin
39Gao, Chuan
40Goel, Anuj
41Hagemeijer, Yanick
42Harris, Sarah E
43He, Meian
44Hsu, Fang-Chi
45Jackson, Anne U
46Kähönen, Mika
47Kasturiratne, Anuradhani
48Komulainen, Pirjo
49Kühnel, Brigitte
50Laguzzi, Federica
51Luan, Jian'an
52Matoba, Nana
53Nolte, Ilja M
54Padmanabhan, Sandosh
55Riaz, Muhammad
56Rueedi, Rico
57Robino, Antonietta
58Said, M. Abdullah
59Scott, Robert A
60Sofer, Tamar
61Stančáková, Alena
62Takeuchi, Fumihiko
63Tayo, Bamidele O
64van der Most, Peter J
65Varga, Tibor V
66Vitart, Veronique
67Wang, Yajuan
68Ware, Erin B
69Warren, Helen R
70Weiss, Stefan
71Wen, Wanqing
72Yanek, Lisa R
73Zhang, Weihua
74Zhao, Jing Hua
75Afaq, Saima
76Amin, Najaf
77Amini, Marzyeh
78Arking, Dan E
79Aung, Tin
80Boerwinkle, Eric
81Borecki, Ingrid
82Broeckel, Ulrich
83Brown, Morris
84Brumat, Marco
85Burke, Gregory L
86Canouil, Mickaël
87Chakravarti, Aravinda
88Charumathi, Sabanayagam
89Ida Chen, Yii-Der
90Connell, John M
91Correa, Adolfo
92de las Fuentes, Lisa
93de Mutsert, Renée
94de Silva, H. Janaka
95Deng, Xuan
96Ding, Jingzhong
97Duan, Qing
98Eaton, Charles B
99Ehret, Georg
100...
jtitlePLoS ONE
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0Feitosa
1Kraja
2Chasman
3Sung
4Winkler
5Ntalla
6Guo
7Franceschini
8Cheng
9Sim
10Vojinovic
11Marten
12Musani
13Li
14Bentley
15Brown
16Schwander
17Richard
18Noordam
19Aschard
20Bartz
21Bielak
22Dorajoo
23Fisher
24Hartwig
25Horimoto
26Lohman
27Manning
28Rankinen
29Smith
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58Said
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60Sofer
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63Tayo
64van der Most
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68Ware
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72Yanek
73Zhang
74Zhao
75Afaq
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78Arking
79Aung
80Boerwinkle
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99Eppinga
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1Aldi T.
2Daniel I.
3Yun J.
4Thomas W.
5Ioanna
6Xiuqing
7Nora
8Ching-Yu
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10Dina
11Jonathan
12Solomon K.
13Changwei
14Amy R.
15Michael R.
16Karen
17Melissa A.
18Raymond
19Hugues
20Traci M.
21Lawrence F.
22Rajkumar
23Virginia
24Fernando P.
25Andrea R. V. R.
26Kurt K.
27Alisa K.
28Tuomo
29Albert V.
30Salman M.
31Mary K.
32Maris
33Mathilde
34Qiuyin
35Archie
36Jin Fang
37Xu
38Jasmin
39Chuan
40Anuj
41Yanick
42Sarah E.
43Meian
44Fang-Chi
45Anne U.
46Mika
47Anuradhani
48Pirjo
49Brigitte
50Federica
51Jian'an
52Nana
53Ilja M.
54Sandosh
55Muhammad
56Rico
57Antonietta
58M. Abdullah
59Robert A.
60Tamar
61Alena
62Fumihiko
63Bamidele O.
64Peter J.
65Tibor V.
66Veronique
67Yajuan
68Erin B.
69Helen R.
70Stefan
71Wanqing
72Lisa R.
73Weihua
74Jing Hua
75Saima
76Najaf
77Marzyeh
78Dan E.
79Tin
80Eric
81Ingrid
82Ulrich
83Morris
84Marco
85Gregory L.
86Mickaël
87Aravinda
88Sabanayagam
89Yii-Der
90John M.
91Adolfo
92Lisa
93Renée
94H. Janaka
95Xuan
96Jingzhong
97Qing
98Charles B.
99Georg
100...
au
0Feitosa, Mary F.
1Kraja, Aldi T.
2Chasman, Daniel I.
3Sung, Yun J.
4Winkler, Thomas W.
5Ntalla, Ioanna
6Guo, Xiuqing
7Franceschini, Nora
8Cheng, Ching-Yu
9Sim, Xueling
10Vojinovic, Dina
11Marten, Jonathan
12Musani, Solomon K.
13Li, Changwei
14Bentley, Amy R.
15Brown, Michael R.
16Schwander, Karen
17Richard, Melissa A.
18Noordam, Raymond
19Aschard, Hugues
20Bartz, Traci M.
21Bielak, Lawrence F.
22Dorajoo, Rajkumar
23Fisher, Virginia
24Hartwig, Fernando P.
25Horimoto, Andrea R. V. R.
26Lohman, Kurt K.
27Manning, Alisa K.
28Rankinen, Tuomo
29Smith, Albert V.
30Tajuddin, Salman M.
31Wojczynski, Mary K.
32Alver, Maris
33Boissel, Mathilde
34Cai, Qiuyin
35Campbell, Archie
36Chai, Jin Fang
37Chen, Xu
38Divers, Jasmin
39Gao, Chuan
40Goel, Anuj
41Hagemeijer, Yanick
42Harris, Sarah E.
43He, Meian
44Hsu, Fang-Chi
45Jackson, Anne U.
46Kähönen, Mika
47Kasturiratne, Anuradhani
48Komulainen, Pirjo
49Kühnel, Brigitte
50Laguzzi, Federica
51Luan, Jian'an
52Matoba, Nana
53Nolte, Ilja M.
54Padmanabhan, Sandosh
55Riaz, Muhammad
56Rueedi, Rico
57Robino, Antonietta
58Said, M. Abdullah
59Scott, Robert A.
60Sofer, Tamar
61Stančáková, Alena
62Takeuchi, Fumihiko
63Tayo, Bamidele O.
64van der Most, Peter J.
65Varga, Tibor V.
66Vitart, Veronique
67Wang, Yajuan
68Ware, Erin B.
69Warren, Helen R.
70Weiss, Stefan
71Wen, Wanqing
72Yanek, Lisa R.
73Zhang, Weihua
74Zhao, Jing Hua
75Afaq, Saima
76Amin, Najaf
77Amini, Marzyeh
78Arking, Dan E.
79Aung, Tin
80Boerwinkle, Eric
81Borecki, Ingrid
82Broeckel, Ulrich
83Brown, Morris
84Brumat, Marco
85Burke, Gregory L.
86Canouil, Mickaël
87Chakravarti, Aravinda
88Charumathi, Sabanayagam
89Ida Chen, Yii-Der
90Connell, John M.
91Correa, Adolfo
92de las Fuentes, Lisa
93de Mutsert, Renée
94de Silva, H. Janaka
95Deng, Xuan
96Ding, Jingzhong
97Duan, Qing
98Eaton, Charles B.
99Ehret, Georg
100...
atitleNovel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
jtitlePLoS ONE
date2018
risdate2018
genrearticle
ristypeJOUR
abstractHeavy 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 x 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 x 10−8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 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.
pubPublic Library of Science
doi10.1371/journal.pone.0198166
urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005576/pdf/
issue6
orcidid0000-0003-0292-5421
volume13
pagese0198166
issn19326203
eissn19326203
oafree_for_read