Lisa de las Fuentes, Washington University School of Medicine in St. Louis
Yun Ju Sung, Washington University School of Medicine in St. Louis
Raymond Noordam, Leids Universitair Medisch Centrum
Thomas Winkler, Universität Regensburg
Mary F. Feitosa, Washington University School of Medicine in St. Louis
Karen Schwander, Washington University School of Medicine in St. Louis
Amy R. Bentley, National Human Genome Research Institute (NHGRI)
Michael R. Brown, University of Texas School of Public Health
Xiuqing Guo, The Lundquist Institute
Alisa Manning, Massachusetts General Hospital
Daniel I. Chasman, Brigham and Women's Hospital
Hugues Aschard, Harvard T.H. Chan School of Public Health
Traci M. Bartz, University of Washington School of Medicine
Lawrence F. Bielak, University of Michigan School of Public Health
Archie Campbell, The University of Edinburgh
Ching Yu Cheng, Singapore Eye Research Institute
Rajkumar Dorajoo, A-Star, Genome Institute of Singapore
Fernando P. Hartwig, Universidade Federal de Pelotas
A. R.V.R. Horimoto, Universidade de São Paulo
Changwei Li, University of Georgia
Ruifang Li-Gao, Leids Universitair Medisch Centrum
Yongmei Liu, Wake Forest University Health Sciences
Jonathan Marten, The University of Edinburgh
Solomon K. Musani, University of Mississippi School of Medicine
Ioanna Ntalla, Barts and The London School of Medicine and Dentistry
Tuomo Rankinen, Pennington Biomedical Research Center
Melissa Richard, McGovern Medical School
Xueling Sim, National University Health System
Albert V. Smith, University of Michigan School of Public Health
Salman M. Tajuddin, National Institute on Aging (NIA)
Bamidele O. Tayo, Loyola University Chicago
Dina Vojinovic, Erasmus MC
Helen R. Warren, Barts and The London School of Medicine and Dentistry

Document Type

Article

Publication Date

6-1-2021

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.

Publication Source (Journal or Book title)

Molecular Psychiatry

First Page

2111

Last Page

2125

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