Interactive effects of genetic variants and oral contraceptive use on depression in the UK Biobank

The study examined the relationship between oral contraceptive (OC) use and depression incidence in young adults. A total of 202,243 participants were followed from birth to age 23.29 years. Results showed that 57.5% of participants initiated OC use and 1.0% received a depression diagnosis. Those who started using OCs had a 20% higher hazard of incident depression compared to non-users. Researchers searched for genetic variants that could moderate this relationship but found no variants with genome-wide significance. Eight variants showed suggestive interaction signals, and two genes (FSIP1 and EHBP1) showed suggestive signals at the gene level, but none reached the genome-wide threshold. The study concludes that if genetic effects on OC-related depression exist, they are likely small and polygenic, meaning there is currently no solid basis for using genetic data in individualized contraception counselling regarding mood-related side effects.