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.
Original language | English |
---|---|
Pages (from-to) | 2111-2125 |
Number of pages | 15 |
Journal | Molecular Psychiatry |
Volume | 26 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2021 |
Bibliographical note
Publisher Copyright:© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Funding
Acknowledgements This project was largely supported by a grant from the U.S. National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health, R01HL118305. A Career Development Award (K25HL121091), also from the NHLBI, enabled Dr. Sung to play a major role on this project. Dr. Kilpeläinen was supported by the Novo Nordisk Foundation (NNF18CC0034900 and NNF17OC0026848). Full set of study-specific funding sources and acknowledgments appear in the Supplementary Material. These authors constitute the writing group: L.d.l.F., Y.J.S., R.N., T.W., M.F.F., K.S., P.B.M., P.W.F., D.C.R., M.F.
Funders | Funder number |
---|---|
National Institutes of Health (NIH) | |
National Heart, Lung, and Blood Institute (NHLBI) | R01HL085251, R01HL118305 |
National Heart, Lung, and Blood Institute (NHLBI) | |
Novo Nordisk Fonden | NNF17OC0026848, NNF18CC0034900 |
Novo Nordisk Fonden |
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Molecular Biology