TY - JOUR
T1 - Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
AU - de las Fuentes, Lisa
AU - Sung, Yun Ju
AU - The LifeLines Cohort Study
AU - Noordam, Raymond
AU - Winkler, Thomas
AU - Feitosa, Mary F.
AU - Schwander, Karen
AU - Bentley, Amy R.
AU - Brown, Michael R.
AU - Guo, Xiuqing
AU - Manning, Alisa
AU - Chasman, Daniel I.
AU - Aschard, Hugues
AU - Bartz, Traci M.
AU - Bielak, Lawrence F.
AU - Campbell, Archie
AU - Cheng, Ching Yu
AU - Dorajoo, Rajkumar
AU - Hartwig, Fernando P.
AU - Horimoto, A. R.V.R.
AU - Li, Changwei
AU - Li-Gao, Ruifang
AU - Liu, Yongmei
AU - Marten, Jonathan
AU - Musani, Solomon K.
AU - Ntalla, Ioanna
AU - Rankinen, Tuomo
AU - Richard, Melissa
AU - Sim, Xueling
AU - Smith, Albert V.
AU - Tajuddin, Salman M.
AU - Tayo, Bamidele O.
AU - Vojinovic, Dina
AU - Warren, Helen R.
AU - Xuan, Deng
AU - Alver, Maris
AU - Boissel, Mathilde
AU - Chai, Jin Fang
AU - Riaz, Muhammad
AU - Verweij, Niek
AU - Amin, Najaf
AU - Ikram, M. Arfan
AU - Kavousi, Maryam
AU - Rueda-Ochoa, Oscar Leonel
AU - Teumer, Alexander
AU - Uitterlinden, André G.
AU - Wang, Ya Xing
AU - Zhao, Wei
AU - Pereira, A. C.
AU - van Duijn, Cornelia M.
AU - Wong, Tien Yin
AU - Rao, Dabeeru C.
AU - Fornage, Myriam
N1 - 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. 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.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85085119426&partnerID=8YFLogxK
U2 - 10.1038/s41380-020-0719-3
DO - 10.1038/s41380-020-0719-3
M3 - Article
C2 - 32372009
AN - SCOPUS:85085119426
SN - 1359-4184
VL - 26
SP - 2111
EP - 2125
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 6
ER -