Familial risk and heritability of depression by age at first diagnosis in Danish twins

Objective: Familial and genetic factors seem to contribute to the development of depression but whether this varies with age at diagnosis remains unclear. We examined the influence of familial factors on the risk of depression by age at first diagnosis. Methods: We included 23 498 monozygotic and 39 540 same-sex dizygotic twins from the population-based Danish Twin Registry, followed from 1977 through 2011 in nationwide registers. We used time-to-event analyses accounting for censoring and competing risk of death to estimate cumulative incidence, casewise concordance, relative recurrence risk, and heritability of first depression by age using monozygotic and same-sex dizygotic twin pairs. Results: During follow-up, a total of 1545 twins were diagnosed with depression. For twins at age 35 or younger at first depression, heritability was estimated to be 24.8% (95% confidence interval [CI], 4.6–43.1%), whereas at age 90 it was 14.7% (95% CI, 3.1–26.3%). The relative recurrence risk was higher at younger ages: At age 35, the risk was 27.7-fold (95% CI, 20.0–35.5) and 6.9-fold (95% CI, 3.9–9.8) higher than the population risk for monozygotic and same-sex dizygotic twins, respectively, while the corresponding numbers were 3.0 (95% CI, 2.3–3.6) and 1.8 (95% CI, 1.3–2.2) at age 90. Heritability seemed similar for male and female twins. Conclusion: Familial risk of depression, caused either by genes or shared environment, seemed to slightly decrease with age at diagnosis and an elevated concordance risk for monozygotic over same-sex dizygotic pairs suggested a genetic contribution to the development of depression.