Gene-age interactions in blood pressure regulation: A large-scale investigation with the CHARGE, Global BPgen, and ICBP consortia.
- Simino, J.
- Shi, G.
- Bis, J.C.
- Chasman, D.I.
- Ehret, G.
- Gu, X.
- Guo, X.
- Hwang, S.J.
- Sijbrands, E.J.G.
- Smith, A.C.M.
- Verwoert, G.
- Bragg-Gresham, J.L.
- Cadby, G.
- Chen, P.
- Cheng, C.
- Corre, T.
- de Boer, R.
- Goel, A.K.
- Johnson, T.
- Khor, C.C.
- Lluís-Ganella, C.
- Luan, J.
- Lyytikäinen, L.-P.
- Nolte, I.M.
- Sim, X.
- Sõber, S.
- van der Most, P.J.
- Verweij, N.
- Zhao, J.
- Amin, N.
- Boerwinkle, E.E.
- Bouchard, C.
- Dehghan, A.
- Eiriksdottir, G.
- Elosua, R.
- Franco, O.H.
- Gieger, C.
- Harris, T.B.
- Hercberg, S.
- Hofman, A.F.
- James, A.L.
- Johnson, A.D.
- Kähönen, M.
- Khaw, K.T.
- Kutalik, Z.
- Larson, M.G.
- Launer, L.J.
- Li, G.
- Liu, J.
- Liu, K.
- Morrison, A.C.
- Navis, G.J.
- Ong, R.T.H.
- Papanicolau, G.J.
- Penninx, B.W.J.H.
- Psaty, B.M.
- Raffel, L.J.
- Raitakari, O.T.
- Rice, K.
- Rivadeneira, F.
- Rose, L.M.
- Sanna, S.
- Scott, R.A.
- Siscovick, D.S.
- Stolk, R.P.
- Uitterlinden, A.G.
- Vaidya, D.
- van der Klauw, M.M.
- Vasan, R.S.
- Vithana, E.N.
- Völker, U.
- Völzke, H.
- Watkins, H.C.
- Young, T.L.
- Aung, T.
- Bochud, M.
- Farrall, M.
- Hartman, C.A.
- Laan, M.
- Lakatta, E.G.
- Lehtimäki, T.
- Loos, R.J.F.
- Lucas, G.
- Meneton, P.
- Palmer, L.J.
- Rettig, R.
- Snieder, H.
- Tai, E.S.
- Teo, Y.Y.
- van der Harst, P.
- Wareham, N.J.
- Wijmenga, C.
- Wong, T.Y.
- Fornage, M.
- Gudnason, V.G.
- Levy, D.
- Palmas, W.R.
- Ridker, P.M.
- Rotter, J.I.
- van Duijn, C.M.
- Witteman, J.C.M.
- Chakravarti, A.
- Rao, D.C.
DOIAbstract
Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10-8) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstr...
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