Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
PLoS ONE 2018 ; 13: e0198166.
Feitosa MF, Kraja AT, Chasman DI, Sung YJ, Winkler TW, Ntalla I, Franceschini N, Cheng CY, Marten J, Musani SK, Richard MA, Noordam R, Bartz TM, Bielak LF, Dorajoo R, Hartwig FP, Manning AK, Rankinen T, Smith AV, Tajuddin SM, Wojczynski MK, Alver M, Campbell A, Divers J, Goel A, Harris SE, Jackson AU, Kähönen M, Kasturiratne A, Komulainen P, Kühnel B, Luan J, Nolte IM, Padmanabhan S, Riaz M, Rueedi R, Robino A, Said MA, Scott RA, Stančáková A, Takeuchi F, Tayo BO, van der Most PJ, Varga TV, Vitart V, Wang Y, Ware EB, Warren HR, Weiss S, 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, Chakravarti A, Connell JM, Correa A, de Mutsert R, Deng X, Ding J, Eaton CB, Ehret G, Eppinga RN, Evangelou E, Faul JD, Felix SB, Forouhi NG, Forrester T, Franco OH, Friedlander Y, Gandin I, Ghanbari M, Gigante B, Hallmans G, Harris TB, Heng CK, Howard BV, Ikram MA, Katsuya T, Khor CC, Kilpeläinen TO, Koh WP, Kubo M, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lehne B, Lewis CE, Mägi R, McKenzie CA, Meitinger T, Metspalu A, Milaneschi Y, Milani L, Mohlke KL, Nalls MA, Nelson CP, Sotoodehnia N, Norris JM, O'Connell JR, Palmer ND, Pedersen NL, Peters A, Peyser PA, Poulter N, Raffel LJ, Raitakari OT, Roll K, Rose LM, Rosendaal FR, Rotter JI, Schreiner PJ, Schupf N, Scott WR, Sever PS, Sidney S, Sitlani CM, Smith JA, Snieder H, Starr JM, Strauch K, Stringham HM, Tang H, Taylor KD, Teo YY, Tham YC, Turner ST, Uitterlinden AG, Vollenweider P, Waldenberger M, Wang L, Wang YX, Williams 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, 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, Zheng W, Bouchard C, Christensen K, Evans MK, Gudnason V, Horta BL, Kardia SLR, Psaty BM, Ridker PM, van Dam RM, Mook-Kanamori DO, Fornage M, Rotimi CN, Cupples LA, Kelly TN, 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, and Levy D
PubMed ID : 29912962
PMCID : PMC6005576
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.