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This large-scale genetic study of over 202,000 UK Biobank participants found that oral contraceptive users had a 20% higher risk of depression in young adulthood compared to non-users, but identified no specific genetic variants that determine who is susceptible to these mood effects. Despite examining genome-wide interactions between genetics and contraceptive use, no genes reached statistical significance for moderating the depression risk associated with oral contraceptives. The findings suggest that if genetic factors do influence individual susceptibility to contraceptive-related depression, the effects are likely too small and complex to be clinically useful for personalized contraceptive counseling.
Why it matters
This research indicates that genetic testing cannot currently help predict which individuals will experience depression as a side effect of oral contraceptives, meaning healthcare providers cannot yet use genetic information to personalize contraceptive recommendations based on mood-related risks. The confirmed association between oral contraceptive use and increased depression risk in young women reinforces the importance of monitoring mental health in contraceptive users.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Background Oral contraceptive (OC) use, particularly during adolescence, may increase depression risk in some individuals, but it remains unclear who is susceptible to mood-related side effects and who is not. We aimed to detect single nucleotide polymorphisms (SNPs) and genes that moderate the effect of OC use on depression in young adulthood using data from the UK Biobank. Methods N=202,243 participants were followed from birth to age 23.29 (SD: 2.58) years. We used Cox models for counting processes to test the association between OC use and incident depression in young adulthood, and conducted a genome-wide-by-drug-interaction study (GWDIS) of SNP by OC use interactions alongside a standard genome-wide association study (GWAS) on incident depression in young adulthood. Results Over half of all participants (57.5%) initiated OC and 1.0% received a depression diagnosis during follow up. OC initiators had a 20% higher hazard of incident depression than non-initiators (HR=1.20, 95% CI=1.04-1.37). No SNPs reached genome-wide significance in the GWDIS, though eight showed suggestive interaction signals (p<1e-5). At the gene level, FSIP1 (p=5.90e-5) and EHBP1 (p=6.47e-5) showed suggestive signals, but none passed the genome-wide threshold. No SNPs reached genome-wide significance in the GWAS. Conclusions We did not find evidence for genetic variants that moderate the association between OC initiation and depression. If such effects exist, they are likely to be small and polygenic, suggesting there is currently no solid basis for using genetic data for individualised contraception counselling concerning mood-based side effects.
Source: Interactive effects of genetic variants and oral contraceptive use on depression in the UK Biobank