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

TitleMulti-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.
Publication TypeJournal Article
Year of Publication2021
AuthorsSun, D, Richard, M, Musani, SK, Sung, YJu, Winkler, TW, Schwander, K, Chai, J-F, Guo, X, Kilpeläinen, TO, Vojinovic, D, Aschard, H, Bartz, TM, Bielak, LF, Brown, MR, Chitrala, K, Hartwig, FP, Horimoto, ARVR, Liu, Y, Manning, A, Noordam, R, Smith, AV, Harris, SE, Kühnel, B, Lyytikäinen, L-P, Nolte, IM, Rauramaa, R, van der Most, PJ, Wang, R, Ware, EB, Weiss, S, Wen, W, Yanek, LR, Arking, DE, Arnett, DK, Barac, A, Boerwinkle, E, Broeckel, U, Chakravarti, A, Chen, Y-DIda, L Cupples, A, Davigulus, ML, Fuentes, Lde Las, de Mutsert, R, de Vries, PS, Delaney, JAC, Roux, AVDiez, Dörr, M, Faul, J, Fretts, AM, Gallo, LC, Grabe, H-J, C Gu, C, Harris, TB, Hartman, CCA, Heikkinen, S, M Ikram, A, Isasi, C, W Johnson, C, Jonas, JBruno, Kaplan, RC, Komulainen, P, Krieger, JE, Levy, D, Liu, J, Lohman, K, Luik, AI, Martin, LW, Meitinger, T, Milaneschi, Y, O'Connell, J, Palmas, WR, Peters, A, Peyser, PA, Pulkki-Raback, L, Raffel, LJ, Reiner, AP, Rice, K, Robinson, JG, Rosendaal, FR, Schmidt, COliver, Schreiner, PJ, Schwettmann, L, Shikany, JM, Shu, X-O, Sidney, S, Sims, M, Smith, JA, Sotoodehnia, N, Strauch, K, E Tai, S, Taylor, K, Uitterlinden, AG, van Duijn, CM, Waldenberger, M, Wee, H-L, Bin Wei, W-, Wilson, G, Xuan, D, Yao, J, Zeng, D, Zhao, W, Zhu, X, Zonderman, AB, Becker, DM, Deary, IJ, Gieger, C, Lakka, TA, Lehtimäki, T, North, KE, Oldehinkel, AJ, Penninx, BWJH, Snieder, H, Wang, Y-X, Weir, DR, Zheng, W, Evans, MK, W Gauderman, J, Gudnason, V, Horta, BL, Liu, C-T, Mook-Kanamori, DO, Morrison, AC, Pereira, AC, Psaty, BM, Amin, N, Fox, ER, Kooperberg, C, Sim, X, Bierut, L, Rotter, JI, Kardia, SLR, Franceschini, N, Rao, DC, Fornage, M
Corporate AuthorsLifeLines Cohort Study
JournalHuman Genetics and Genomics Advances
ISSN Number2666-2477
Keywordsblood pressure traits


p>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.

Citation Key12126
PubMed ID34734193
PubMed Central IDPMC8562625
Grant ListR01 HL105756 / HL / NHLBI NIH HHS / United States
R01 HL118305 / HL / NHLBI NIH HHS / United States