Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
Feitosa MF; Kraja AT; Chasman DI; Sung YJ; Winkler TW; Ntalla I; Guo XQ; Franceschini N; Cheng CY; Sim XL; Vojinovic D; Marten J; Musani SK; Li CW; 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 QY; Campbell A; Chai JF; Chen X; Divers J; Gao C; Goel A; Hagemeijer Y; Harris SE; He MI; Hsu FC; Jackson AU; Kahonen M; Kasturiratne A; Komulainen P; Kuhnel B; Laguzzi F; Luan J; Matoba N; Nolte IM; Padmanabhan S; Riaz M; Rueedi R; Robino A; Said MA; Scott RA; Sofer T; Stancakova A; Takeuchi F; Tayo BO; van der Most PJ; Varga TV; Vitart V; Wang YJ; Ware EB; Warren HR; Weiss S; Wen WQ; Yanek LR; Zhang WH; 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; Fuentes LDL; de Mutsert R; de Silva HJ; Deng X; Ding J; Duan Q; Eaton CB; Ehret G; Eppinga RN; Evangelou E; Fau JD; Felix SB; Forouhi NG; Forrester T; Franco OH; Friedlander Y; Gandin I; Gao H; Ghanbari M; Gigante B; Gu CC; Gu DF; Hagenaars SP; Hallmans G; Harris TB; He J; Heikkinen S; Heng CK; Hirata M; Howard BV; Ikram MA; John U; Katsuya T; Khor CC; Kilpelainen TO; Koh WP; Krieger JE; Kritchevsky SB; Kubo M; Kuusisto J; Lakka TA; Langefeld CD; Langenberg C; Launer LJ; Lehne B; Lewis CE; Li YZ; Lin S; Liu JJ; Liu JM; Loh M; Louie T; Magi 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 LH; Wang YX; Bin Wei W; Williams C; Yao J; Yu CZ; 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; Lehtimaki T; Study LC; Magnusson PKE; Oldehinkel AJ; Penninx BWJH; Poiasek 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 TC; Zheng W; Bouchard C; Christensen K; Evans MK; Gudnason V; Horta BL; Kardia SLR; Liu YM; Pereira AC; Psaty BM; Ridker PM; van Dam RM; Gauderman WJ; Zhu XF; 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; Levy D; Province MA; Munroe PB; Rao DC
Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
PUBLIC LIBRARY SCIENCE
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042719468
https://urn.fi/URN:NBN:fi-fe2021042719468
Tiivistelmä
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 approximate to 131 K 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 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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