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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 ; Poveda, Alaitz LU ; Franks, Paul LU and Fornage, Myriam (2020) In Molecular Psychiatry
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... (More)
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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. (Less)
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keywords
adult, ancestry group, article, blood pressure regulation, central nervous system, controlled study, diastolic blood pressure, dissection, female, follow up, human, kidney function, male, mean arterial pressure, mental capacity, meta analysis, protein function, pulse pressure, signal transduction, social status, structure activity relation, systolic blood pressure
in
Molecular Psychiatry
publisher
Nature Publishing Group
external identifiers
  • scopus:85085119426
  • pmid:32372009
ISSN
1359-4184
DOI
10.1038/s41380-020-0719-3
language
English
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yes
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68ba99eb-1ebd-429c-9334-6fe650418f71
date added to LUP
2020-06-23 13:03:23
date last changed
2020-12-29 01:52:49
@article{68ba99eb-1ebd-429c-9334-6fe650418f71,
  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 &lt; 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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.},
  author       = {de las Fuentes, Lisa and Poveda, Alaitz and Franks, Paul and Fornage, Myriam},
  issn         = {1359-4184},
  language     = {eng},
  month        = {05},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Psychiatry},
  title        = {Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci},
  url          = {http://dx.doi.org/10.1038/s41380-020-0719-3},
  doi          = {10.1038/s41380-020-0719-3},
  year         = {2020},
}