Age and cohort differences in the association between polygenic scores and psychological distress: evidence from the 1958 and 1970 British Birth Cohorts

Psychological distress is influenced by genetic, environmental, and age-related factors. Although cohort differences in psychological distress have been evidenced, it is unclear whether these reflect genetic effects. We estimated the association between polygenic scores (PGS) for psychological distress and observed distress across adulthood in the 1958 National Child Development Study (1958c) and 1970 British Cohort Study (1970c). Psychological distress was measured using the Malaise Inventory between ages 23 and 50 across nine occasions. PGS were derived from a genome-wide association study of depressive symptoms. Age-specific associations were examined using linear regression, and cohort-stratified multilevel mixed-effects models tested PGS interactions with age and sex. Distress scores were higher in the 1970c and in females. In both cohorts, PGS were positively associated with psychological distress, with effect sizes increasing with age; incremental R² rose from 1.83% to 2.86% in the 1958c and from 1.44% to 2.16% in the 1970c. The 1958c displayed a steeper age-related increase in genetic effects, while the 1970c showed larger genetic effects in early adulthood (ages 26–30) that converged at older ages. A PGS-by-sex interaction was identified in the 1958c only, with females showing stronger genetic effects than males. Genetic liability to psychological distress exerts a modest but increasing influence across adulthood. Cohort differences appear driven more by environmental than genetic factors. The sex-specific genetic effect in the 1958c but not the 1970c suggests the interplay between genetic liability and sex varies across historical contexts, highlighting the need for sex-specific and cohort-specific approaches in future research.