The Genetic Epidemiology of Treated Major Depression in Sweden

Villumsen

et al. 2020

Acta Psychiatr Scand

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.

Section: Discussionsupporting

confidence: 91%

“…We also addressed censoring and took competing risk of death into account when we estimated the heritability of depression by age of depression onset (24). Because of few early-onset cases, the measures based on within-pair comparisons were only provided from age 35.…”

Section: Methodsmentioning

confidence: 99%

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

Villumsen

et al. 2020

Acta Psychiatr Scand

“…Some predictors of mental health-related work disability have been identified (Halonen et al, 2017 them. The association between parents' mental disorders and offspring's early work disability due to mental disorders may be direct as indicated by the evidence on heritability of mental disorders (Franic, Middeldorp, Dolan, Ligthart, & Boomsma, 2010;Kendler, Ohlsson, Lichtenstein, Sundquist, & Sundquist, 2018). However, the association is also likely affected by the offspring's circumstances in childhood and adolescence.…”

Section: Introductionmentioning

confidence: 99%

Pathways from parental mental disorders to offspring's work disability due to depressive or anxiety disorders in early adulthood—The 1987 Finnish Birth Cohort

et al. 2018

Background Parental mental disorders have been shown to predict offspring's mental health problems. We examined whether pathways from parental mental disorders to offspring's psychiatric work disability in early adulthood are mediated through offspring's mental disorders and social disadvantage in adolescence. Methods Study population consisted of the 1987 Finnish Birth Cohort. Data on parents’ psychiatric care or work disability due to mental diagnosis between 1987 and 2000 and the cohort participants’ health and social factors between 2001 and 2005 were derived from administrative national registers. From 2006 through 2015, 52,182 cohort participants were followed for admittance of psychiatric work disability due to depressive or anxiety disorders. First, we applied a pathway analysis to examine the occurrence of each path. We then used mediation analysis to assess the proportion of association between parental mental disorders and work disability mediated by offspring's health and social disadvantage. Results The pathway model indicated that the association from parental mental disorders to offspring's work disability due to depressive or anxiety disorder is through mental disorders and social disadvantage in adolescence. Odds Ratio for the total effect of parental mental disorders on offspring's psychiatric work disability was 1.85 (95% confidence interval [CI] 1.46–2.34) in the model including offspring's mental disorders that mediated this association by 35%. Corresponding results were 1.86 (95% CI 1.47–2.35) and 28% for social disadvantage in adolescence. Conclusions These findings suggest that intergenerational determination of work disability due to mental disorders could be addressed by actions supporting mental health and social circumstances in adolescence.

“…Much of the literature exploring heritability by component has focused on recurrence, which has consistently been shown to increase the heritability of MD (9,11,12,19,40).…”

Section: Discussionmentioning

confidence: 99%

“…Recent advances in biobank level data and genetic research allow us to explore the biological basis of diverse MDD presentations. Major depression (MD) has a significant heritable component, with estimates in the range of 20 and 50% (9)(10)(11)(12). It is a polygenic trait, meaning the genetic variance is explained partly by multiple common genetic variants of individually small effect in the population (13).…”

Section: Introductionmentioning

confidence: 99%

What’s in a diagnosis? A genetic decomposition of major depression

Jermy

Glanville

Coleman

et al. 2020

Preprint

Determining a diagnosis of major depressive disorder (MDD) is complex, involving consideration and rating of a variety of different components. These include number of symptoms over an agreed threshold, symptom duration, functional impairment, persistence of symptoms within an episode, and symptom recurrence. While these components are generally accepted amongst physicians, it is unknown whether they reflect partly distinct biology between phenotypes. The aim of this study was to investigate how the genetic aetiology varies in the presence of different MDD components.Thirty-two depression phenotypes which systematically incorporate the MDD components were created using the mental health questionnaire data within the UK Biobank. SNP-based heritabilities and genetic correlations with three previously defined major depression phenotypes were calculated (broad depression, Psychiatric Genomics Consortium (PGC) defined depression and 23andMe, Inc. self-reported depression) and differences between estimates analysed.All phenotypes were heritable (h2SNP range: 0.102 – 0.162) and showed substantial genetic correlations with other major depression phenotypes (Rg range: 0.651 – 0.894 (PGC); 0.652 – 0.837 (23andMe); 0.699 – 0.900 (broad depression)). The requirement for 5 or more symptoms and for a long episode duration had the strongest effect on SNP-based heritability, in the positive and negative direction respectively (1.4% average increase; 2.7% average decrease). No significant differences were noted between genetic correlations.While there is some variation, the two cardinal symptoms, depressed mood and anhedonia, largely reflect the genetic aetiology of phenotypes incorporating more MDD components. These components may appropriately index for severity, however, the genetic component between phenotypes incorporating none and all components is comparable.