Liu S Y, Walter S, Marden J, Rehkopf D H, Kubzansky L D, Nguyen T, Glymour M M
Harvard Center for Population and Development Studies, 9 Bow Street, Cambridge, MA 02138, USA.
UCSF School of Medicine, Department of Epidemiology & Biostatistics, 185 Berry Street, San Francisco, CA 94107, USA.
Soc Sci Med. 2015 Feb;127:150-8. doi: 10.1016/j.socscimed.2014.09.009. Epub 2014 Sep 6.
The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D.
2型糖尿病(T2D)和肥胖症的患病率最近急剧上升。这些常见疾病可能源于多种遗传、社会人口统计学和环境风险因素的相互作用。虽然先前的研究发现遗传风险和教育程度是这些疾病的有力预测因素,但迄今为止,很少有研究考察它们的联合效应。本研究调查教育是否会改变遗传背景与2型糖尿病(T2D)和肥胖症风险之间的关联。利用健康与退休研究(HRS,n = 8398)中来自非西班牙裔白人的数据,我们测试了教育是否会改变肥胖症和T2D的遗传风险,抵消遗传效应;对于因其他(未观察到的)原因而具有高风险的个体,即处于糖化血红蛋白(HbA1c)和体重指数(BMI)较高百分位数的个体,这种效应是否更大;以及效应是否因性别而异。我们使用糖化血红蛋白(HbA1c)水平测量T2D风险,使用体重指数(BMI)测量肥胖风险。我们分别根据关于单核苷酸多态性(SNP)的最新可用信息构建了肥胖症和糖尿病的单独遗传风险评分(GRS),这些SNP被确认为BMI(29个SNP)和糖尿病风险(39个SNP)的全基因组显著预测因素。具有受教育年限的线性回归模型表明,与具有高中学历的人相比,受教育年限较多的人遗传风险对HbA1c的影响较小,而高中以下学历的人遗传风险对HbA1c的影响较大。分位数回归模型表明,GRS×教育效应沿着HbA1c结果分布系统性增加;例如,在第10百分位数处,GRS×受教育年限交互系数为-0.01(95%置信区间 = -0.03, 0.00),而在第90百分位数处为-0.03(95%置信区间 = -0.!7, 0.00)。这些结果表明,教育可能是对T2D遗传易感性反应中异质性的一个重要社会经济来源。