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

MedStar author(s):

1932-6203

Name of journal: PloS oneAbstract: 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.All authors: Afaq S, Alver M, Amin N, Amini M, Arking DE, Aschard H, Aung T, Bartz TM, Becker DM, Bentley AR, Bielak LF, Boehnke M, Boerwinkle E, Boissel M, Borecki I, Bouchard C, Bowden DW, Broeckel U, Brown M, Brown MR, Brumat M, Burke GL, Cai Q, Campbell A, Canouil M, Caulfield MJ, Chai JF, Chakravarti A, Chambers JC, Charumathi S, Chasman DI, Chen X, Cheng CY, Christensen K, Connell JM, Correa A, Cupples LA, de Las Fuentes L, de Mutsert R, de Silva HJ, Deary IJ, Deng X, Ding J, Divers J, Dorajoo R, Duan Q, Eaton CB, Ehret G, Elliott P, Eppinga RN, Esko T, Evangelou E, Evans MK, Farrall M, Faul JD, Feitosa MF, Felix SB, Fisher V, Fornage M, Forouhi NG, Forrester T, Fox ER, Franceschini N, Franco OH, Franks PW, Freedman BI, Friedlander Y, Froguel P, Gandin I, Gao C, Gao H, Gasparini P, Gauderman WJ, Ghanbari M, Gieger C, Gigante B, Goel A, Gu CC, Gu D, Gudnason V, Guo X, Hagemeijer Y, Hagenaars SP, Hallmans G, Harris SE, Harris TB, Hartwig FP, Hayward C, He J, He M, Heikkinen S, Heng CK, Hirata M, Horimoto ARVR, Horta BL, Howard BV, Hsu FC, Ida Chen YD, Ikram MA, InterAct Consortium, Jackson AU, John U, Jonas JB, Kahonen M, Kamatani Y, Kardia SLR, Kasturiratne A, Kato N, Katsuya T, Kelly TN, Khor CC, Kilpelainen TO, Koh WP, Komulainen P, Kooner JS, Kooperberg C, Kraja AT, Krieger JE, Kritchevsky SB, Kubo M, Kuhnel B, Kutalik Z, Kuusisto J, Laakso M, Laguzzi F, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Laurie CC, Leander K, Lehne B, Lehtimaki T, Levy D, Lewis CE, Li C, Li Y, Lin S, Liu J, Liu J, Liu Y, Loh M, Lohman KK, Louie T, Luan J, Magi R, Magnusson PKE, Manning AK, Marten J, Matoba N, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Momozawa Y, Mook-Kanamori DO, Morrison AC, Munroe PB, Musani SK, Nalls MA, Nelson CP, Nolte IM, Noordam R, Norris JM, Ntalla I, O'Connell JR, Oldehinkel AJ, Padmanabhan S, Palmas W, Palmer ND, Pedersen NL, Penninx BWJH, Pereira AC, Perls T, Peters A, Peyser PA, Polasek O, Porteous DJ, Poulter N, Province MA, Psaty BM, Raffel LJ, Raitakari OT, Rankinen T, Rao DC, Rauramaa R, Riaz M, Rice K, Richard MA, Ridker PM, Robino A, Roll K, Rose LM, Rosendaal FR, Rotimi CN, Rotter JI, Rueedi R, Said MA, Samani NJ, Schmidt CO, Schreiner PJ, Schupf N, Schwander K, Scott J, Scott RA, Scott WR, Sever PS, Shi Y, Shu XO, Sidney S, Sim X, Sims M, Sitlani CM, Smith AV, Smith JA, Snieder H, Sofer T, Sotoodehnia N, Stancakova A, Starr JM, Strauch K, Stringham HM, Study LC, Sung YJ, Tai ES, Tajuddin SM, Takeuchi F, Tan NYQ, Tang H, Taylor KD, Tayo BO, Teo YY, Tham YC, Turner ST, Uitterlinden AG, van Dam RM, van der Harst P, van der Most PJ, van Duijn CM, Varga TV, Vitart V, Vojinovic D, Vollenweider P, Wagenknecht LE, Waldenberger M, Wang L, Wang Y, Wang YX, Ware EB, Wareham NJ, Warren HR, Watkins H, Wei WB, Weir DR, Weiss S, Wen W, Wickremasinghe AR, Williams C, Winkler TW, Wojczynski MK, Wong TY, Wu T, Yanek LR, Yao J, Yu C, Yuan JM, Zhang W, Zhao JH, Zhao W, Zheng W, Zhu X, Zonderman ABFiscal year: FY2018Digital Object Identifier:

https://dx.doi.org/10.1371/journal.pone.0198166

Date added to catalog: 2018-07-06

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Title notes ( 3 )

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Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	29912962	Available		29912962

Available online through MWHC library: 2006 - present

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.

English