Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
File(s)
Accepted version
Accepted version
Author(s)
Type
Journal Article
Abstract
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
Date Issued
2020-05-05
Date Acceptance
2020-03-24
Citation
Molecular Psychiatry, 2020, 26, pp.2111-2125
ISSN
1359-4184
Publisher
Springer Nature [academic journals on nature.com]
Start Page
2111
End Page
2125
Journal / Book Title
Molecular Psychiatry
Volume
26
Copyright Statement
© The Author(s), under exclusive licence to Springer Nature Limited 2020. The final publication is available at Springer via https://doi.org/10.1038/s41380-020-0719-3
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000530592500002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/L01341X/1
MR/R023484/1
MR/S019669/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Neurosciences
Psychiatry
Neurosciences & Neurology
CORONARY-HEART-DISEASE
SOCIOECONOMIC-STATUS
RISK-FACTORS
CARDIOVASCULAR-DISEASE
ESSENTIAL-HYPERTENSION
C825T POLYMORPHISM
SOCIAL-CLASS
ASSOCIATION
EXPRESSION
VARIANTS
Publication Status
Published
Date Publish Online
2020-05-05