Genetic and environmental risk factors for major depression in UK women and their association with telomere length longitudinally.

BACKGROUND

Major depressive disorder (MDD) is more prevalent in women and associated with shorter telomere length, a marker of biological ageing, and an increased risk of age-related disease. However, the precise influence of depression-related genetic and environmental risk factors on telomere dynamics remains a topic of debate.

METHODS

We examined leukocyte relative telomere length (RTL) and longitudinal telomere attrition in 958 women (median age: 58 years) from the TwinsUK cohort. RTL was measured using quantitative PCR from up to four timepoints. Associations with self-reported depression, antidepressant use, lifestyle and socioeconomic factors, and polygenic risk scores (PGS) for MDD and comorbid age-related diseases were assessed using linear mixed models.

RESULTS

Over a median 6-year follow-up, telomere length declined annually by 1.3 % of baseline RTL. Depression showed a borderline association with shorter RTL (p = 0.06), while a nominal association was observed between antidepressant use and shorter RTL (p = 0.02), replicating previous findings. No significant associations were observed for PGS related to MDD. PGS for coronary artery disease was associated with shorter RTL (p = 0.02), while other trait PGS showed inconsistent associations with RTL or attrition. Higher waist-to-hip ratio was associated with faster telomere attrition longitudinally (p = 0.01).

CONCLUSIONS

Our findings suggest depression and its genetic liability are not directly associated with telomere length or attrition in older women. In contrast, waist-to-hip ratio, a modifiable factor, was linked to accelerated telomere shortening, pointing to central adiposity as a potential intervention target with relevance for both mental and physical health.