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

Lifelines Cohort Study, Daokun Sun, Melissa Richard, Solomon K Musani, Yun Ju Sung, Thomas W Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Michael R Brown, Kumaraswamy Chitrala, Fernando P Hartwig, Andrea R V R Horimoto, Yongmei Liu, Alisa K ManningRaymond Noordam, Albert V Smith, Sarah E Harris, Brigitte Kühnel, Leo-Pekka Lyytikäinen, Ilja M Nolte, Rainer Rauramaa, Peter J van der Most, Rujia Wang, Erin B Ware, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Dan E Arking, Donna K Arnett, Ana Barac, Eric Boerwinkle, Ulrich Broeckel, Aravinda Chakravarti, Yii-Der Ida Chen, L Adrienne Cupples, Martha L Davigulus, Lisa de Las Fuentes, Renée de Mutsert, Paul S de Vries, Catharina C A Hartman, Wei Zhao, Albertine J Oldehinkel, Brenda W J H Penninx, Harold Snieder, Ya-Xing Wang, M Fornage*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)
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Samenvatting

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.

Originele taal-2English
TijdschriftHGG advances
Volume2
Nummer van het tijdschrift1
DOI's
StatusPublished - 14-jan-2021

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