Accès ouvert déclaré
2024
review
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
O. Pedersen, James R Staley, M.E. Jørgensen, T. Tuomi, R. Rauramaa, Robin Young, Artur Akbarov, I. Brandslund, Carmen Fava, Lawrence F. Bielak, Frida Renström, Digna R. Velez Edwards, L. Lannfelt, Josh Bis, Alena Stanáková, Elena V. Feofanova, M. Perola, A.F. Dominiczak, Tiina Laatikainen, Luca A. Lotta, Annemari Käräjämäki, A.S. Havulinna, Stella Trompet, Jessica D. Faul, C.P. Cabrera, Marcus Dörr, Lisa W. Martin, Rainer Rettig, T. Hansen, D.J. Liu, Eero Kajantie, Matt J. Neville, Xueling Sim, Shih-Jen Hwang, C. Menni, A. Mahajan, S.M. Willems, U. Thorsteinsdottir, David Mosén-Ansorena, Neil Poulter, S.T. Turner, J.A. Smith, M. Richard, Guðmundur Þorgeirsson, Bing Yu, P. Surendran, He Gao, Peter Sever, Guðmar Þorleifsson, Daníel F. Guðbjartsson, Ιωάννα Ντάλλα, K. Cho, Jaana Lindström, N W Rayner, Savita Karthikeyan, G.J. Papanicolaou, Yunfeng Lu, Jie Yao, J.H. Cartwright, T.V. Varga, H.A. Koistinen, N. Grarup, Martin G. Larson, W. Zhang, James Eales, C.T. Have, J Connell, Philip S. Tsao, L. Chen, Marie Moitry, H.R. Warren, Dirk S. Paul, L.L. Bonnycastle, Johan Sundström, Anil K. Giri, C.N.A. Palmer, A.V. Smith, S.E. Harris, Rob J. de Boer, Gerardo Heiss, Awais Rasheed, Ioanna Tzoulaki, Changfu Yao, Kari Kuulasmaa, Tõnu Esko, Pim van der Harst, Olga Giannakopoulou, G. Nadkarni, Eralda Asllanaj, Giovanni Veronesi, Peter S. Braund, Stefanie Aeschbacher, G. Malerba, B.P. Prins, Stephen Burgess, C Christensen, James E. Peters, Jennifer E. Huffman, Stefan Blankenberg, Jianhua Zhao, Patrick Sulem, Csaba P. Kövesdy, R. Li-Gao, E.W. Daw, Borbála Mifsud, Hao Mei, Peter van der Meer, A. Poveda, Isobel D. Stewart, Katrine Laura Rasmussen, Jukka Kontto, Sune F. Nielsen, J. Luan, I‐Te Lee, Vickie Braithwaite, Allan Linneberg, Julia L. Cook, J. Michael Gaziano, Engilbert Sigurðsson, Won‐Jae Lee, Jacques E. Rossouw, T.G. Richardson, T. Ferreira, Martina Müller‐Nurasyid, Nuno Sepúlveda, N. Franceschini, A.T. Kraja, Wei Zhao, Xiuqing Guo, Pamela J. Schreiner, F. Giulianini, Wei Zhao, Yan V. Sun, J. Bork-Jensen, Eric B. Fauman, P.L. Auer, Sébastien Thériault, Nicholas G. D. Masca, Guðný Eiríksdóttir, E. Evangelou, Jacklyn N. Hellwege, M.L. Grove, Renée de Mutsert, Niek Verweij, D.O. Mook-Kanamori, M. Kamat, A.-E. Farmaki, Elisabetta Trabetti, Anna Helgadóttir, T. Skaaby, V. Tragante, G. Hallmans, Najim Lahrouchi, F. Karpe, Jennifer A. Brody, Christopher N. Foley, Guillaume Paré, Stavroula Kanoni, F. Drenos, Reedik Mägi
10Citations signalées, ce qui n’est pas une note de qualité
0Institutions déclarées
0Pays d’affiliation déclarés
Le résumé fourni par la source
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.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
La source scientifique ouverte est momentanément indisponible.
Les sujets associés
Nutrition, Genetics, and DiseaseGenomics and Rare Diseases