英国剑桥大学Joanna M. M. Howson、伦敦玛丽女王大学Patricia B. Munroe等研究人员合作通过对130万个人进行荟萃分析，发现与血压调节相关的稀有变异。相关论文于2020年11月23日在线发表于国际学术期刊《自然—遗传学》。
Title: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
Author: Praveen Surendran, Elena V. Feofanova, Najim Lahrouchi, Ioanna Ntalla, Savita Karthikeyan, James Cook, Lingyan Chen, Borbala Mifsud, Chen Yao, Aldi T. Kraja, James H. Cartwright, Jacklyn N. Hellwege, Ayush Giri, Vinicius Tragante, Gudmar Thorleifsson, Dajiang J. Liu, Bram P. Prins, Isobel D. Stewart, Claudia P. Cabrera, James M. Eales, Artur Akbarov, Paul L. Auer, Lawrence F. Bielak, Joshua C. Bis, Vickie S. Braithwaite, Jennifer A. Brody, E. Warwick Daw, Helen R. Warren, Fotios Drenos, Sune Fallgaard Nielsen, Jessica D. Faul, Eric B. Fauman, Cristiano Fava, Teresa Ferreira, Christopher N. Foley, Nora Franceschini, He Gao, Olga Giannakopoulou, Franco Giulianini, Daniel F. Gudbjartsson, Xiuqing Guo, Sarah E. Harris, Aki S. Havulinna, Anna Helgadottir, Jennifer E. Huffman, Shih-Jen Hwang, Stavroula Kanoni, Jukka Kontto, Martin G. Larson, Ruifang Li-Gao, Jaana Lindstrm, Luca A. Lotta, Yingchang Lu, Jianan Luan, Anubha Mahajan, Giovanni Malerba, Nicholas G. D. Masca, Hao Mei, Cristina Menni, Dennis O. Mook-Kanamori, David Mosen-Ansorena
Abstract: 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<5×108), 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.