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

Harvard

de Las Fuentes, L, Sung, YJ, Noordam, R, Winkler, T, Feitosa, MF, Schwander, K, Bentley, AR, Brown, MR, Guo, X, Manning, A, Chasman, DI, Aschard, H, Bartz, TM, Bielak, LF, Campbell, A, Cheng, C-Y, Dorajoo, R, Hartwig, FP, Horimoto, ARVR, Li, C, Li-Gao, R, Liu, Y, Marten, J, Musani, SK, Ntalla, I, Rankinen, T, Richard, M, Sim, X, Smith, AV, Tajuddin, SM, Tayo, BO, Vojinovic, D, Warren, HR, Xuan, D, Alver, M, Boissel, M, Chai, J-F, Chen, X, Christensen, K, Divers, J, Evangelou, E, Gao, C, Girotto, G, Harris, SE, He, M, Hsu, F-C, Kühnel, B, Laguzzi, F, Li, X, Kilpeläinen, TO & LifeLines Cohort Study 2021, 'Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci', Molecular Psychiatry, vol. 26, pp. 2111-2125. https://doi.org/10.1038/s41380-020-0719-3

APA

de Las Fuentes, L., Sung, Y. J., Noordam, R., Winkler, T., Feitosa, M. F., Schwander, K., Bentley, A. R., Brown, M. R., Guo, X., Manning, A., Chasman, D. I., Aschard, H., Bartz, T. M., Bielak, L. F., Campbell, A., Cheng, C-Y., Dorajoo, R., Hartwig, F. P., Horimoto, A. R. V. R., ... LifeLines Cohort Study (2021). Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Molecular Psychiatry, 26, 2111-2125. https://doi.org/10.1038/s41380-020-0719-3

Vancouver

de Las Fuentes L, Sung YJ, Noordam R, Winkler T, Feitosa MF, Schwander K et al. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. Molecular Psychiatry. 2021;26:2111-2125. https://doi.org/10.1038/s41380-020-0719-3

Author

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. / Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. In: Molecular Psychiatry. 2021 ; Vol. 26. pp. 2111-2125.

Bibtex

@article{c0c3822966c4446b9cb5e8828080687f,
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 = "{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 Ching-Yu Cheng 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 Jin-Fang Chai 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 Fang-Chi Hsu and Brigitte K{\"u}hnel and Federica Laguzzi and Xiaoyin Li and Kilpel{\"a}inen, {Tuomas O} and {LifeLines Cohort Study}",
year = "2021",
doi = "10.1038/s41380-020-0719-3",
language = "English",
volume = "26",
pages = "2111--2125",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "nature publishing group",

}

RIS

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