RESUMO
Background: Socioeconomic Status (SES) is a potent environmental determinant of health. To our knowledge, no assessment of genotype-environment interaction has been conducted to consider the joint effects of socioeconomic status and genetics on risk for metabolic disease. We analyzed data from the Mexican American Family Studies (MAFS) to evaluate the hypothesis that genotype-by-environment interaction (GxE) is an essential determinant of variation in risk factors for metabolic syndrome (MS). Methods: We employed a maximum likelihood estimation of the decomposition of variance components to detect GxE interaction. After excluding individuals with diabetes and individuals on medication for diabetes, hypertension, or dyslipidemia, we analyzed 12 MS risk factors: fasting glucose (FG), fasting insulin (FI), 2-h glucose (2G), 2-h insulin (2I), body mass index (BMI), waist circumference (WC), leptin (LP), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), total serum cholesterol (TSC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Our SES variable used a combined score of Duncan's socioeconomic index and education years. Heterogeneity in the additive genetic variance across the SES continuum and a departure from unity in the genetic correlation coefficient were taken as evidence of GxE interaction. Hypothesis tests were conducted using standard likelihood ratio tests. Results: We found evidence of GxE for fasting glucose, 2-h glucose, 2-h insulin, BMI, and triglycerides. The genetic effects underlying the insulin/glucose metabolism component of MS are upregulated at the lower end of the SES spectrum. We also determined that the household variance for systolic blood pressure decreased with increasing SES. Conclusion: These results show a significant change in the GxE interaction underlying the major components of MS in response to changes in socioeconomic status. Further mRNA sequencing studies will identify genes and canonical gene pathways to support our molecular-level hypotheses.
RESUMO
Background: Socioeconomic status (SES) is a potent environmental determinant of health. To our knowledge, no assessment of genotype-environment interaction has been conducted to consider the joint effects of socioeconomic status and genetics on risk for cardiovascular disease (CVD). We analyzed Mexican American Family Studies (MAFS) data to evaluate the hypothesis that genotype-by-environment interaction (GxE) is an important determinant of variation in CVD risk factors. Methods: We employed a linear mixed model to investigate GxE in Mexican American extended families. We studied two proxies for CVD [Pooled Cohort Equation Risk Scores/Framingham Risk Scores (FRS/PCRS) and carotid artery intima-media thickness (CA-IMT)] in relation to socioeconomic status as determined by Duncan's Socioeconomic Index (SEI), years of education, and household income. Results: We calculated heritability for FRS/PCRS and carotid artery intima-media thickness. There was evidence of GxE due to additive genetic variance heterogeneity and genetic correlation for FRS, PCRS, and CA-IMT measures for education (environment) but not for household income or SEI. Conclusion: The genetic effects underlying CVD are dynamically modulated at the lower end of the SES spectrum. There is a significant change in the genetic architecture underlying the major components of CVD in response to changes in education.