Genetic predisposition and alcohol consumption are risk factors for increased blood pressure (BP), but their interactions influencing BP remain understudied. We conducted population-specific and cross-population meta-analyses of genome-wide gene-alcohol (GxAlc) interactions affecting BP in >1.1M individuals from multiple populations. We identified 46 GxAlc interaction loci for BP, including 21 from one-degree-of-freedom interaction tests (PGxAlc<5x10-8; or <0.05/Meff, Meff independent BP associations at P<10-5), and 25 from two-degree-of-freedom tests of main and interaction effects (PGxAlc<0.05/M2df, M2df independent 2df-associations at P2df<5x10-8), including 7 novel and 39 known BP loci. The 12q24 locus highlights the genetic effect of BRAP-rs11066001 on BP, being ~6 times larger in current drinkers than in non-drinkers. Gene prioritization with 46 GxAlc loci identified 15 genes with ≥3 lines of evidence (location, literature, druggability, functional/regulatory annotation, or pathway analyses). Several loci showed sex- and population-specific effects and revealed biological pathways of alcohol's influence on BP, suggesting mechanisms underlying alcohol-induced hypertension.
Discovery of gene-alcohol interaction loci influencing blood pressure in 1.1 million individuals from multiple populations / Feitosa, M; Schwander, K; Miller, C; Kraja, A; Bentley, A; Brown, M; De Hesselle, H; Noordam, R; Lee, S; Nagarajan, P; Wang, H; Giri, A; Ammous, F; Bartz, T; Batini, C; Brandenburg, Jt; Breyer, M; Cordell, H; Corley, J; Dimotrov, L; Do, A; Du, J; Giulianini, F; Grace, C; Gudmundsdottir, V; Guo, X; Harris, S; Hasbani, N; Herold, J; Hikino, K; Hofer, E; Horimoto, A; Hsu, Fc; Huang, Z; Jackson, A; Kang, Ch; Laguzzi, F; Lakka, T; Lefevre, C; Luan, J; Lyytikäinen, Lp; Meirhaeghe, A; Muntaner, M; Nakatochi, M; Nardone, Gg; Nolte, I; Nutile, T; Palmer, N; Patki, A; Pecori, A; Rao, V; Richmond, A; Richter, M; Sanghvi, M; Santin, A; Stringham, H; Takeuchi, F; Tan, Ya; Tang, J; Teder-Laving, M; Trofimova, O; Trompet, S; Van Der Most, P; Wang, Yx; Wang, Z; Wang, Y; Wang, W; Ware, E; Weiss, S; Westerman, K; Yu, C; Zhu, W; Ansari, May; Anugu, P; Argoty-Pantoja, A; Attia, J; Banas, B; Bazzano, L; Bis, J; Boger, C; Brody, J; Broeckel, U; Campbell, H; Campbell, A; Cennamo, P; Checkley, W; Chee, Ml; Chen, G; Chen, Yd; Coley, K; Collins, S; Dallongeville, J; De Silva, Hj; Dupont, C; Edwards, T; Enzinger, C; Faul, J; Silva, Lf; Gepner, A; Goel, A; Gorski, M; Graff, M; Gu, Cc; He, J; Heikkinen, S; Hill-Burns, E; Hung, A; Hunt, S; Irvin, M; Kähönen, M; Kardia, S; Kho, M; Koistinen, H; Kolčić, I; Komulainen, P; Krieger, Je; Launer, L; Levy, D; Liu, J; Mccormick, J; Mcneil, J; Milaneschi, Y; Miranda, J; North, K; Oravilahti, A; Pattie, A; Peyser, P; Pianigiani, G; Raffel, L; Raitakari, O; Ramsay, M; Redkar, S; Redmond, P; Ridker, P; Rosendaal, F; Ruggiero, D; Russ, T; Sabanayagam, C; Scartozzi, A; Schmidt, R; Scott, L; Scott, R; Shenkin, S; Smit, R; Smith, Ja; Soh, Zd; Spedicati, B; Stott, D; Sun, Q; Sze, G; Tai, Es; Tesolin, P; Triatin, R; Vaitinadin, Ns; Van Dam, R; Vaucher, J; Völker, U; Völzke, H; Wang, C; Warren, H; Wickremasinghe, R; Van Dijk, Kw; Xue, C; Yamamoto, K; Yao, J; Yokota, M; Zimmermann, M; Amouyel, P; Below, J; Bergmann, S; Bernabe-Ortiz, A; Boehnke, M; Boua, P; Study, Lc; Bowden, D; Chasman, D; Cheng, Cy; Ciullo, M; Concas, Mp; Cox, Sr; Dauchet, L; Deary, I; Felix, S; Fox, E; Franceschini, N; Freedman, B; Gasparini, P; Girotto, G; Gudnason, V; Hayward, C; Heid, I; Holliday, E; Ichihara, S; John, C; Jonas, J; Jukema, Jw; Kals, M; Kato, N; Keavney, B; Kelly, T; Laakso, M; Lacaze, P; Lange, L; Leander, K; Lee, S; Lehtimäki, T; Li, C; Liu, Ct; Loos, R; Penninx, B; Pereira, A; Polasek, O; Psaty, B; Rauramaa, R; Rotimi, C; Rotter, J; Rudan, I; Schmidt, H; Sim, X; Snieder, H; Stark, K; Terao, C; Wagenknecht, L; Wareham, N; Watkins, H; Weir, D; Young, K; Zhao, W; Gauderman, W; Morrison, A; Fornage, M; Chen, H; O'Connell, J; Manning, A; De Vries, P; Fuentes, Ll; Rao, D; Munroe, P; Province, M; Winkler, T.. - (In corso di stampa), pp. "-"-"-". [Epub ahead of print] [10.21203/rs.3.rs-9283196/v1]
Discovery of gene-alcohol interaction loci influencing blood pressure in 1.1 million individuals from multiple populations
Nardone GG;Richter M;Santin A;Wang W;Pianigiani G;Scartozzi A;Spedicati B;Tesolin P;Concas MP;Gasparini P;Girotto G;Rudan I;Zhao W;Winkler T.
In corso di stampa
Abstract
Genetic predisposition and alcohol consumption are risk factors for increased blood pressure (BP), but their interactions influencing BP remain understudied. We conducted population-specific and cross-population meta-analyses of genome-wide gene-alcohol (GxAlc) interactions affecting BP in >1.1M individuals from multiple populations. We identified 46 GxAlc interaction loci for BP, including 21 from one-degree-of-freedom interaction tests (PGxAlc<5x10-8; or <0.05/Meff, Meff independent BP associations at P<10-5), and 25 from two-degree-of-freedom tests of main and interaction effects (PGxAlc<0.05/M2df, M2df independent 2df-associations at P2df<5x10-8), including 7 novel and 39 known BP loci. The 12q24 locus highlights the genetic effect of BRAP-rs11066001 on BP, being ~6 times larger in current drinkers than in non-drinkers. Gene prioritization with 46 GxAlc loci identified 15 genes with ≥3 lines of evidence (location, literature, druggability, functional/regulatory annotation, or pathway analyses). Several loci showed sex- and population-specific effects and revealed biological pathways of alcohol's influence on BP, suggesting mechanisms underlying alcohol-induced hypertension.Pubblicazioni consigliate
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