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 language | English |
|---|---|
| Article number | e0198166 |
| Journal | PLoS ONE |
| Volume | 13 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2018 |
| Externally published | Yes |
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In: PLoS ONE, Vol. 13, No. 6, e0198166, 06.2018.
Research output: Contribution to journal › Article › peer-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
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AU - Vojinovic, Dina
AU - Marten, Jonathan
AU - Musani, Solomon K.
AU - Li, Changwei
AU - Bentley, Amy R.
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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
N1 - Publisher Copyright: © 2018 Public Library of Science. All Rights Reserved.
PY - 2018/6
Y1 - 2018/6
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
C2 - 29912962
AN - SCOPUS:85049155160
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0198166
ER -