ArticleEuropean journal of human genetics : EJHG2015
Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene.
Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses.BMC research notes · 2018Pooled it
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- It's Not the Genes OR the Environment, It's the Genes AND the Environment!Journal of the American Heart Association · 2021Article
- High expression of CD52 in adipocytes: a potential therapeutic target for obesity with type 2 diabetes.Aging · 2021Article
- The -514C>T polymorphism in the LIPC gene modifies type 2 diabetes risk through modulation of HDL-cholesterol levels in Mexicans.Journal of endocrinological investigation · 2021Article
- Pleiotropic genetic influence on birth weight and childhood obesity.Scientific reports · 2021Article
- Nipping Adipocyte Inflammation in the Bud.Immunometabolism · 2021Article
- Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants.Translational psychiatry · 2020Article
- Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants.Neurobiology of disease · 2020Article
- R230C but not - 565C/T variant of the ABCA1 gene is associated with type 2 diabetes in Mexicans through an effect on lowering HDL-cholesterol levels.Journal of endocrinological investigation · 2020Article
- Testing gene-environment interactions for rare and/or common variants in sequencing association studies.PloS one · 2020Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps = 7.14E-09 to 2.33E-08, uncorrected; Ps = 1.99E-07 to 5.18E-07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps = 0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate = 0.26, P = 0.033, 95% CI = 0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate = 0.004, P = 0.34, 95% CI = -0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values = 0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease.
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