Hagenbeek Fiona A, Richmond Anne, Tamlander Max, Detrois Kira, Yang Zhiyu, Hartonen Tuomo, McCartney Daniel L, Marioni Riccardo E, Martikainen Pekka, Mars Nina, Ganna Andrea, Ripatti Samuli
Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
medRxiv. 2025 Sep 4:2025.09.02.25334913. doi: 10.1101/2025.09.02.25334913.
Both socioeconomic circumstances and genetic predisposition shape disease risk, yet their joint contribution across diseases has not been systematically examined. We studied 19 high-burden diseases in 743,194 participants (729,928 European; 13,266 non-European ancestry) from FinnGen, the UK Biobank, and Generation Scotland. Higher educational attainment was associated with lower risk of most conditions, but with higher risk of most common cancers. These associations were largely independent of disease-specific polygenic scores (PGSs). For seven out of 19 diseases, PGSs showed stronger effects among individuals with high education. Joint inclusion of education and PGSs modestly improved prediction for 14 and 10 out of 19 diseases in FinnGen and the UK Biobank, respectively. PGS associations were consistent across ancestries, whereas education effects were less stable; results using an alternative socioeconomic measure were directionally similar but smaller. Our findings highlight the distinct and partly interacting contributions of socioeconomic and genetic factors to disease risk.
社会经济环境和遗传易感性都会影响疾病风险，但它们对各种疾病的共同影响尚未得到系统研究。我们对来自芬兰基因库（FinnGen）、英国生物银行（UK Biobank）和苏格兰一代研究（Generation Scotland）的743194名参与者（729928名欧洲血统；13266名非欧洲血统）中的19种高负担疾病进行了研究。受教育程度较高与大多数疾病的较低风险相关，但与大多数常见癌症的较高风险相关。这些关联在很大程度上独立于疾病特异性多基因评分（PGS）。在19种疾病中的7种疾病中，PGS在高学历个体中显示出更强的作用。将教育程度和PGS共同纳入模型，分别使芬兰基因库和英国生物银行中19种疾病中的14种和10种疾病的预测得到适度改善。PGS关联在不同血统中是一致的，而教育程度的影响则不太稳定；使用另一种社会经济指标的结果在方向上相似，但影响较小。我们的研究结果突出了社会经济和遗传因素对疾病风险的不同且部分相互作用的影响。
