Sun Daokun, Richard Melissa, Musani Solomon K, Sung Yun Ju, Winkler Thomas W, Schwander Karen, Chai Jin Fang, Guo Xiuqing, Kilpeläinen Tuomas O, Vojinovic Dina, Aschard Hugues, Bartz Traci M, Bielak Lawrence F, Brown Michael R, Chitrala Kumaraswamy, Hartwig Fernando P, Horimoto Andrea R V R, Liu Yongmei, Manning Alisa K, Noordam Raymond, Smith Albert V, Harris Sarah E, Kühnel Brigitte, Lyytikäinen Leo-Pekka, Nolte Ilja M, Rauramaa Rainer, van der Most Peter J, Wang Rujia, Ware Erin B, Weiss Stefan, Wen Wanqing, Yanek Lisa R, Arking Dan E, Arnett Donna K, Barac Ana, Boerwinkle Eric, Broeckel Ulrich, Chakravarti Aravinda, Chen Yii-Der Ida, Cupples L Adrienne, Davigulus Martha L, de las Fuentes Lisa, de Mutsert Renée, de Vries Paul S, Delaney Joseph A C, Roux Ana V Diez, Dörr Marcus, Faul Jessica D, Fretts Amanda M, Gallo Linda C, Grabe Hans Jörgen, Gu C Charles, Harris Tamara B, Hartman Catharina C A, Heikkinen Sami, Ikram M Arfan, Isasi Carmen, Johnson W Craig, Jonas Jost Bruno, Kaplan Robert C, Komulainen Pirjo, Krieger Jose E, Levy Daniel, Liu Jianjun, Lohman Kurt, Luik Annemarie I, Martin Lisa W, Meitinger Thomas, Milaneschi Yuri, O'Connell Jeff R, Palmas Walter R, Peters Annette, Peyser Patricia A, Pulkki-Råback Laura, Raffel Leslie J, Reiner Alex P, Rice Kenneth, Robinson Jennifer G, Rosendaal Frits R, Schmidt Carsten Oliver, Schreiner Pamela J, Schwettmann Lars, Shikany James M, Shu Xiao-Ou, Sidney Stephen, Sims Mario, Smith Jennifer A, Sotoodehnia Nona, Strauch Konstantin, Tai E Shyong, Taylor Kent, Uitterlinden André G, van Duijn Cornelia M, Waldenberger Melanie, Wee Hwee-Lin, Wei Wen-Bin, Wilson Gregory, Xuan Deng, Yao Jie, Zeng Donglin, Zhao Wei, Zhu Xiaofeng, Zonderman Alan B, Becker Diane M, Deary Ian J, Gieger Christian, Lakka Timo A, Lehtimäki Terho, North Kari E, Oldehinkel Albertine J, Penninx Brenda W J H, Snieder Harold, Wang Ya-Xing, Weir David R, Zheng Wei, Evans Michele K, Gauderman W James, Gudnason Vilmundur, Horta Bernardo L, Liu Ching-Ti, Mook-Kanamori Dennis O, Morrison Alanna C, Pereira Alexandre C, Psaty Bruce M, Amin Najaf, Fox Ervin R, Kooperberg Charles, Sim Xueling, Bierut Laura, Rotter Jerome I, Kardia Sharon L R, Franceschini Nora, Rao Dabeeru C, Fornage Myriam
Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
These authors contributed equally to this work.
HGG Adv. 2021 Jan 14;2(1). doi: 10.1016/j.xhgg.2020.100013. Epub 2020 Oct 31.
Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (), synaptic function and neurotransmission (), as well as genes previously implicated in neuropsychiatric or stress-related disorders (). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
已知心理和社会因素会影响血压（BP）以及高血压和相关心血管疾病的风险。为了确定新的血压相关基因座，我们进行了全基因组关联荟萃分析，研究收缩压、舒张压、脉压和平均动脉压，并考虑了基因变异与三种心理社会因素（抑郁症状、焦虑症状和社会支持）的相互作用。分析采用两阶段设计，样本来自5个祖先群体的多达128,894名成年人。在第1阶段和第2阶段的联合荟萃分析中，我们确定了59个基因座（p值<5e-8），其中包括9个新的血压相关基因座。新的关联大多在脉压中观察到，在平均动脉压中观察到的较少。在非洲血统中确定了5个新基因座，除一个外，所有基因座都显示出与至少一种心理社会因素的相互作用模式。新基因座的功能注释支持免疫反应相关基因、突触功能和神经传递相关基因以及先前与神经精神或应激相关疾病相关的基因发挥主要作用。这些发现强调了在血压基因发现中考虑心理和社会因素的重要性，尤其是在非欧洲人群中。
