Thio Chris H L, van Zon Sander K R, van der Most Peter J, Snieder Harold, Bültmann Ute, Gansevoort Ron T
Am J Epidemiol. 2021 May 4;190(5):864-874. doi: 10.1093/aje/kwaa237.
Both genetic predisposition and low educational attainment (EA) are associated with higher risk of chronic kidney disease. We examined the interaction of EA and genetic risk in kidney function outcomes. We included 3,597 participants from the Prevention of Renal and Vascular End-Stage Disease Cohort Study, a longitudinal study in a community-based sample from Groningen, the Netherlands (median follow-up, 11 years; 1997-2012). Kidney function was approximated by obtaining estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C. Individual longitudinal linear eGFR trajectories were derived from linear mixed models. Genotype data on 63 single-nucleotide polymorphisms, with known associations with eGFR, were used to calculate an allele-weighted genetic score (WGS). EA was categorized into high, medium, and low. In ordinary least squares analysis, higher WGS and lower EA showed additive effects on reduced baseline eGFR; the interaction term was nonsignificant. In analysis of eGFR decline, the significant interaction term suggested amplification of genetic risk by low EA. Adjustment for known renal risk factors did not affect our results. This study presents the first evidence of gene-environment interaction between EA and a WGS for eGFR decline and provides population-level insights into the mechanisms underlying socioeconomic disparities in chronic kidney disease.
遗传易感性和低教育程度均与慢性肾病的较高风险相关。我们研究了教育程度与基因风险在肾功能结局中的相互作用。我们纳入了来自预防肾和血管终末期疾病队列研究的3597名参与者，该研究是一项基于荷兰格罗宁根社区样本的纵向研究（中位随访时间为11年；1997 - 2012年）。通过血清肌酐和胱抑素C计算估计肾小球滤过率（eGFR）来估算肾功能。个体纵向线性eGFR轨迹由线性混合模型得出。利用63个与eGFR已知关联的单核苷酸多态性的基因型数据来计算等位基因加权基因评分（WGS）。教育程度分为高、中、低三类。在普通最小二乘法分析中，较高的WGS和较低的教育程度对降低的基线eGFR显示出相加效应；交互项不显著。在eGFR下降分析中，显著的交互项表明低教育程度会放大基因风险。对已知肾脏风险因素进行校正并不影响我们的结果。本研究首次证明了教育程度与eGFR下降的WGS之间存在基因 - 环境相互作用，并为慢性肾病社会经济差异背后的机制提供了人群水平的见解。
