ArticlePsychological medicine2025
Genetic risk scores of psychiatric phenotypes are associated with depression risk in a prospective Dutch population-based cohort.
Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGenetic risk scores hold potential for predicting depression in the general population. These scores must be validated for their associations with relevant characteristics of depression-related phenotypes, such as severity. We validated a genome-wide risk score (GRS) and a restricted polygenic risk score (PRS) for depression based on a meta-analysis of three genome-wide association studies and assessed their associations with depression in three subcohorts of middle-aged and older adults from the Dutch population-based Rotterdam Study.
methodsOf participants with genotype data, 9,198 had longitudinally measured data (mean follow-up: 11.3 years) on three depression-related phenotypes (depressive symptoms, depressive syndrome, and major depressive disorder). Generalized linear models estimated the associations of standardized GRS and PRS with depression phenotypes per subcohort and were then meta-analyzed. One unit of the GRS/PRS represents 1 standard deviation, following
resultsA one unit higher GRS and PRS were associated with any longitudinally measured depression phenotype (odds ratio (OR)
conclusionsThe GRS and PRS for depression showed modest associations across multiple depression-related phenotypes in a population-based setting. The strength of associations generally increased with the severity of the phenotype. While effect sizes were generally larger for GRS compared to PRS, the difference was mostly not statistically significant.
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