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Surendran, P.* ; Feofanova, E.V.* ; Lahrouchi, N.* ; Ntalla, I.* ; Karthikeyan, S.* ; Cook, J.* ; Chen, L.* ; Mifsud, B.* ; Yao, C.* ; Kraja, A.T.* ; Cartwright, J.H.* ; Hellwege, J.N.* ; Giri, A.* ; Tragante, V.* ; Thorleifsson, G.* ; Liu, D.J.* ; Prins, B.P.* ; Stewart, I.D.* ; Cabrera, C.P.* ; Eales, J.M.* ; Akbarov, A.* ; Auer, P.L.* ; Bielak, L.F.* ; Bis, J.C.* ; Braithwaite, V.S.* ; Brody, J.A.* ; Daw, E.W.* ; Warren, H.R.* ; Drenos, F.* ; Nielsen, S.F.* ; Faul, J.D.* ; Fauman, E.B.* ; Fava, C.* ; Ferreira, T.* ; Foley, C.N.* ; Franceschini, N.* ; Gao, H.* ; Giannakopoulou, O.* ; Giulianini, F.* ; Gudbjartsson, D.F.* ; Guo, X.* ; Harris, S.E.* ; Havulinna, A.S.* ; Helgadottir, A.* ; Huffman, J.E.* ; Hwang, S.J.* ; Kanoni, S.* ; Kontto, J.* ; Larson, M.G.* ; Li-Gao, R.* ; Lindström, J.* ; Lotta, L.A.* ; Lu, Y.* ; Luan, J.* ; Mahajan, A.* ; Malerba, G.* ; Masca, N.G.D.* ; Mei, H.* ; Menni, C.* ; Mook-Kanamori, D.O.* ; Mosen-Ansorena, D.* ; Müller-Nurasyid, M. ; Paré, G.* ; Paul, D.S.* ; Perola, M.* ; Poveda, A.* ; Rauramaa, R.* ; Richard, M.* ; Richardson, T.G.* ; Sepúlveda, N.* ; Sim, X.* ; Smith, A.V.* ; Smith, J.A.* ; Staley, J.R.* ; Stanáková, A.* ; Sulem, P.* ; Thériault, S.* ; Thorsteinsdottir, U.* ; Trompet, S.* ; Varga, T.V.* ; Velez Edwards, D.R.* ; Veronesi, G.* ; Weiss, S.* ; Willems, S.M.* ; Yao, J.* ; Young, R.* ; Yu, B.* ; Zhang, W.* ; Zhao, J.H.* ; Zhao, W.* ; Evangelou, E.* ; Aeschbacher, S.* ; Asllanaj, E.* ; Blankenberg, S.* ; Bonnycastle, L.L.* ; Bork-Jensen, J.* ; Brandslund, I.* ; Braund, P.S.* ; Cho, K.* ; Christensen, C.* ; Connell, J.* ; de Mutsert, R.* ; Dominiczak, A.* ; Dörr, M.* ; Eiriksdottir, G.* ; Farmaki, A.-E.* ; Gaziano, J.M.* ; Grarup, N.* ; Grove, J.* ; Hallmans, G.* ; Hansen, T.* ; Have, C.T.* ; Heiss, G.* ; Jørgensen, M.E.* ; Jousilahti, P.* ; Kajantie, E.* ; Kamat, M.* ; Käräjämäki, A.* ; Karpe, F.* ; Koistinen, H.A.* ; Kovesdy, C.P.* ; Kuulasmaa, K.* ; Laatikainen, T.* ; Lannfelt, L.* ; Lee, I-T.* ; Lee, W.-J.* ; Linneberg, A.* ; Martin, L.W.* ; Moitry, M.* ; Nadkarni, G.* ; Zeggini, E. ; Charchar, F.J.* ; Wareham, N.J.* ; Newton-Cheh, C.* ; Munroe, P.B.* ; Howson, J.M.M.*

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Nat. Genet. 52, 1314–133 (2020)
Postprint DOI PMC
Open Access Green
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association; Mendelian Randomization; Common Variants; Identifies Common; Loci; Risk; Frequency; Traits; Hypertension; Genetics
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 52, Issue: 12, Pages: 1314–133 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Translational Genomics (ITG)
Grants RCUK | Medical Research Council (MRC)
British Heart Foundation (BHF)