Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits
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Sun, DaokunRichard, 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
Date
2020-10-31Journal
HGG AdvancesPublisher
Elsevier Ltd.Type
Article
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https://doi.org/10.1016/j.xhgg.2020.100013https://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.Identifier to cite or link to this item
http://hdl.handle.net/10713/17086ae974a485f413a2113503eed53cd6c53
10.1016/j.xhgg.2020.100013
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