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

Abstract

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.

Association of Familial Aggregation of Major Depression With Risk of Major Depression

“…21 Siblings and twin studies have shown inconsistency in sex differences in heritability of MD. 15,20,28,34 These differing findings could be due to methodological is- sues, as our study population was sampled in an unselected population using registry data, while the US study recruited participants based on volunteering, which often causes lack of representativeness to the general population. The findings could also be affected by the measurement of MD varying from diagnoses by physicians registered in hospital records to assessments using, for example, the Beck Depression Inventory II, which may be subject to different levels of detection related to sex.…”

“…Additionally, the timing of MD in family members may be important as childhood and adolescence may be sensitive periods with shared environment with parents and siblings. Finally, women are twice as likely as men to experience MD, but these findings are inconsistent as some studies report no difference in MD risk between the sexes …”

“…It has been suggested that the heritability of MD varies with age of familial MD onset, 15 with early-onset MD being more prominent among individuals with a family history. [16][17][18] Additionally, the timing of MD in family members may be important as childhood and adolescence may be sensitive periods with shared environment with parents and siblings.…”

“…Finally, women are twice as likely as men to experience MD, [19][20][21] but these findings are inconsistent as some studies report no difference in MD risk between the sexes. 14,15 Consequently, to understand the mechanisms behind aggregation of MD within families, more research is needed including information on which family relations experience the greatest aggregation and whether sensitive periods and sex differences exist.…”

Intrauterine testosterone exposure and depression risk in opposite-sex and same-sex twins, a Danish register study

“…The twin population was relatively old at first diagnosis possible because they might have been treated earlier in general practice, but in a previous study on the same twin sample (Wium-Andersen et al, 2020) we evaluated the representativeness of our measure of incident depression in a supplementary analysis, including a population-based 5% sample of the non-twin Danish population. We also compared our estimates with a comprehensive study of the lifetime risk of mental disorders in Denmark (Momen et al, 2020), using the same follow-up period from 2000 to 2011.…”