Genetic Risk Assessment of Kidney Function Decline Using Polygenic Risk Score

Le résumé fourni par la source

Background: Genome-wide association studies (GWAS) have identified multiple genetic polymorphisms associated with kidney dysfunction, suggesting the involvement of polygenic inheritance in CKD. Polygenic risk scores (PRS) are indicator of individual disease risk that consider multiple genetic variations. This study aimed to evaluate the utility of PRS to predict CKD development and progression in Japanese general populations. Methods: We conducted a cross-sectional study using the Shika resident cohort (n=895) and a longitudinal study using the Toshiba occupational cohort (n=6,769) in Japan. PRS for kidney dysfunciton were developed using GWAS data from East Asian populations. The kidney outcomes were defined as eGFR <60 ml/min/1.73 m2 and a 30% decline in eGFR. We investigated the association between PRS and eGFR declines using logistic regression and Cox proportional hazards models adjusted for baseline covariates. Results: The mean (SD) age was 62 (11) and 40 (8) years, proportion of men was 45% and 91%, and mean eGFR was 71.5 (14.1) and 81.8 (12.8) ml/min/1.73 m2 in the resident and occupational cohorts, respectively. There were 157 (18%) participants with eGFR <60 ml/min/1.73 m2 in the resident cohort and 1,593 (24%) and 364 (5%) participants who reached eGFR <60 ml/min/1.73 m2 and 30% eGFR decline during follow-up in the occupational cohort. Higher PRS was associated with increased risk of eGFR <60 ml/min/1.73 m2 (resident: OR per 1SD 1.55, 95%CI 1.28-1.89, p<0.001; occupational: HR per 1SD 1.16, 1.10-1.22,p<0.001) as well as 30% eGFR decline (occupational: HR 1.12, 1.01-1.25,p=0.034). These associations remained consistent across age, sex, body mass index, blood pressure, HbA1c, and urinary protein subgroups (p for interaction >0.05). The addition of PRS to conventional prediction models improved the discrimination of eGFR decline risk. Conclusion: PRS are associated with kidney function decline risk in Japanese general populations, independent of traditional risk factors. These findings support that PRS may be useful for personalized genetic risk assessment for CKD development and progression. This approach could enable early identification of high-risk individuals and implementation of preventive strategies in genetically susceptible populations.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.