Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. / de Las Fuentes, Lisa; Sung, Yun Ju; Noordam, Raymond; Winkler, Thomas; Feitosa, Mary F; Schwander, Karen; Bentley, Amy R; Brown, Michael R; Guo, Xiuqing; Manning, Alisa; Chasman, Daniel I; Aschard, Hugues; Bartz, Traci M; Bielak, Lawrence F; Campbell, Archie; Cheng, Ching-Yu; Dorajoo, Rajkumar; Hartwig, Fernando P; Horimoto, A R V R; Li, Changwei; Li-Gao, Ruifang; Liu, Yongmei; Marten, Jonathan; Musani, Solomon K; Ntalla, Ioanna; Rankinen, Tuomo; Richard, Melissa; Sim, Xueling; Smith, Albert V; Tajuddin, Salman M; Tayo, Bamidele O; Vojinovic, Dina; Warren, Helen R; Xuan, Deng; Alver, Maris; Boissel, Mathilde; Chai, Jin-Fang; Chen, Xu; Christensen, Kaare; Divers, Jasmin; Evangelou, Evangelos; Gao, Chuan; Girotto, Giorgia; Harris, Sarah E; He, Meian; Hsu, Fang-Chi; Kühnel, Brigitte; Laguzzi, Federica; Li, Xiaoyin; Kilpeläinen, Tuomas O; LifeLines Cohort Study.
In: Molecular Psychiatry, Vol. 26, 2021, p. 2111-2125.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - 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 - Chen, Xu
AU - Christensen, Kaare
AU - Divers, Jasmin
AU - Evangelou, Evangelos
AU - Gao, Chuan
AU - Girotto, Giorgia
AU - Harris, Sarah E
AU - He, Meian
AU - Hsu, Fang-Chi
AU - Kühnel, Brigitte
AU - Laguzzi, Federica
AU - Li, Xiaoyin
AU - Kilpeläinen, Tuomas O
AU - LifeLines Cohort Study
PY - 2021
Y1 - 2021
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.
U2 - 10.1038/s41380-020-0719-3
DO - 10.1038/s41380-020-0719-3
M3 - Journal article
C2 - 32372009
VL - 26
SP - 2111
EP - 2125
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
ER -
ID: 241055304