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    Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits

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    Author
    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
    Show allShow less

    Date
    2020-10-31
    Journal
    HGG Advances
    Publisher
    Elsevier Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1016/j.xhgg.2020.100013
    https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/34734193/
    Abstract
    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 (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
    Keyword
    psychosocial factors
    Blood Pressure--genetics
    Genome-Wide Association Study
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17086
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.xhgg.2020.100013
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