@article{71d17586d078451d919757cd0878edf2,
title = "Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci",
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.",
author = "{Lifelines Cohort Study} and {de las Fuentes}, Lisa and Sung, {Yun Ju} and Raymond Noordam and Thomas Winkler and Feitosa, {Mary F.} and Karen Schwander and Bentley, {Amy R.} and Brown, {Michael R.} and Xiuqing Guo and Alisa Manning and Chasman, {Daniel I.} and Hugues Aschard and Bartz, {Traci M.} and Bielak, {Lawrence F.} and Archie Campbell and Cheng, {Ching Yu} and Rajkumar Dorajoo and Hartwig, {Fernando P.} and Horimoto, {A. R.V.R.} and Changwei Li and Ruifang Li-Gao and Yongmei Liu and Jonathan Marten and Musani, {Solomon K.} and Ioanna Ntalla and Tuomo Rankinen and Melissa Richard and Xueling Sim and Smith, {Albert V.} and Tajuddin, {Salman M.} and Tayo, {Bamidele O.} and Dina Vojinovic and Warren, {Helen R.} and Deng Xuan and Maris Alver and Mathilde Boissel and Chai, {Jin Fang} and Xu Chen and Kaare Christensen and Jasmin Divers and Evangelos Evangelou and Chuan Gao and Giorgia Girotto and Harris, {Sarah E.} and Meian He and Hsu, {Fang Chi} and Yanek, {Lisa R.} and Arking, {Dan E.} and Dhananjay Vaidya and Becker, {Diane M.}",
note = "Funding Information: 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. Kilpel{\"a}inen 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. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = jun,
doi = "10.1038/s41380-020-0719-3",
language = "English (US)",
volume = "26",
pages = "2111--2125",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "6",
}