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

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Citation: HGG Advances. 2(1), 2021 Jan 14.PMID: 34734193Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: IN PROCESS -- NOT YET INDEXEDYear: 2021Name of journal: HGG advancesAbstract: 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.All authors: Amin N, Arking DE, Arnett DK, Aschard H, Barac A, Bartz TM, Becker DM, Bielak LF, Bierut L, Boerwinkle E, Broeckel U, Brown MR, Chai JF, Chakravarti A, Chen YI, Chitrala K, Cupples LA, Davigulus ML, de Las Fuentes L, de Mutsert R, de Vries PS, Deary IJ, Delaney JAC, Dorr M, Evans MK, Faul JD, Fornage M, Fox ER, Franceschini N, Fretts AM, Gallo LC, Gauderman WJ, Gieger C, Grabe HJ, Gu CC, Gudnason V, Guo X, Harris SE, Harris TB, Hartman CCA, Hartwig FP, Heikkinen S, Horimoto ARVR, Horta BL, Ikram MA, Isasi C, Johnson WC, Jonas JB, Kaplan RC, Kardia SLR, Kilpelainen TO, Komulainen P, Kooperberg C, Krieger JE, Kuhnel B, Lakka TA, Lehtimaki T, Levy D, Lifelines Cohort Study, Liu CT, Liu J, Liu Y, Lohman K, Luik AI, Lyytikainen LP, Manning AK, Martin LW, Meitinger T, Milaneschi Y, Mook-Kanamori DO, Morrison AC, Musani SK, Nolte IM, Noordam R, North KE, O'Connell JR, Oldehinkel AJ, Palmas WR, Penninx BWJH, Pereira AC, Peters A, Peyser PA, Psaty BM, Pulkki-Raback L, Raffel LJ, Rao DC, Rauramaa R, Reiner AP, Rice K, Richard M, Robinson JG, Rosendaal FR, Rotter JI, Roux AVD, Schmidt CO, Schreiner PJ, Schwander K, Schwettmann L, Shikany JM, Shu XO, Sidney S, Sim X, Sims M, Smith AV, Smith JA, Snieder H, Sotoodehnia N, Strauch K, Sun D, Sung YJ, Tai ES, Taylor K, Uitterlinden AG, van der Most PJ, van Duijn CM, Vojinovic D, Waldenberger M, Wang R, Wang YX, Ware EB, Wee HL, Wei WB, Weir DR, Weiss S, Wen W, Wilson G, Winkler TW, Xuan D, Yanek LR, Yao J, Zeng D, Zhao W, Zheng W, Zhu X, Zonderman ABFiscal year: FY2021Digital Object Identifier: Date added to catalog: 2022-02-22
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Journal Article MedStar Authors Catalog Article 34734193 Available 34734193

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.

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