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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Author:
  • Lisa de las Fuentes
  • Alaitz Poveda
  • Paul Franks
  • Myriam Fornage
Publishing year: 2020-05-05
Language: English
Publication/Series: Molecular Psychiatry
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Keywords

  • Public Health, Global Health, Social Medicine and Epidemiology
  • adult
  • ancestry group
  • article
  • blood pressure regulation
  • central nervous system
  • controlled study
  • diastolic blood pressure
  • dissection
  • female
  • follow up
  • human
  • kidney function
  • male
  • mean arterial pressure
  • mental capacity
  • meta analysis
  • protein function
  • pulse pressure
  • signal transduction
  • social status
  • structure activity relation
  • systolic blood pressure

Other

Epub
  • Genetic and Molecular Epidemiology
  • ISSN: 1359-4184
E-mail: alaitz [dot] poveda [dot] 6461 [at] med [dot] lu [dot] se

Postdoctoral fellow

Genetic and Molecular Epidemiology

+46 40 39 10 32

CRC 60-13-024

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00