Age of onset and family history as indicators of polygenic risk for major depression

Abstract

Background The extent to which earlier age of onset (AO) is a reflection of increased genetic risk for major depression (MD) is still unknown. Previous biometrical research has provided mixed empirical evidence for the genetic overlap of AO with MD. If AO is demonstrated to be relevant to molecular polygenic risk for MD, incorporation of AO as a phenotype could enhance future genetic studies. Methods This research estimated the SNP-based heritability of AO in the China, Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) case-control sample (N = 9854, MD case n = 4,927). Common SNP heritability of MD was also examined across both high and low median-split AO groups, and best linear unbiased predictor (BLUP) scores of polygenic risk, in split-halves, were used to predict AO. Distributions of genetic risk across early and late AO were compared, and presence of self-reported family history of MD was also examined as a predictor of AO. Results AO was not significantly heritable and polygenic risk derived from the aggregated effects of common genetic variants did not significantly predict AO in any analysis. AO was modestly but significantly lower in cases with a first-degree genetic family history of MD. Conclusions Findings indicate that AO is associated with greater self-reported genetic risk for MD in cases, yet not associated with common variant polygenic risk for MD. Future studies of early MD may benefit more from the examination of important moderating variables such as early life events.

Suicidal thoughts and attempts in First Nations communities: links to parental Indian residential school attendance across development

“…31 Likewise, adult offspring of parents with mood disorders and a history of suicidal behavior reported a lower mean age of onset of suicidal ideation if they experienced childhood adversity, 24 and earlier age of onset for depressive symptoms as adults. 23,25,31,32 Studies that distinguished between the onset of depressive symptoms in childhood (before 12) or early adolescence (12)(13)(14) v. later adolescence (15)(16)(17)(18) have revealed that earlier onset is linked with a greater risk for chronic suicidal behaviors, mental health problems and substance use in adulthood. [33][34][35][36][37] Considering the chronic childhood adversity faced by many IRS survivors, and how this influenced the abilities of some to provide adequate environments for their children, 8,9,19 it would be expected that adults with a parent who attended IRS would be at risk for higher levels of mental health issues, and would also be more likely to have these difficulties earlier in life.…”

“…4 Parental childhood adversity has been linked with an earlier age of onset of psychological distress and suicidal behavior in non-Indigenous samples. [23][24][25] If this is the case within Indigenous populations affected by IRSs, it would be expected that those with a parent who attended IRS would be at an elevated risk for suicidal thoughts or attempts earlier in life, which could be a contributor to the differential rates of suicide evident in younger v. older age cohorts. Much of the research exploring the intergenerational effects of IRSs has focused on assessing these relationships in adult samples, 8,17 and we are unaware of any research assessing how parental IRS attendance interacts with age to influence mental health outcomes during adolescence or childhood.…”

“…Parental childhood adversity has been linked with an earlier age of onset of psychological distress and suicidal behavior in non-Indigenous samples 23 25 If this is the case within Indigenous populations affected by IRSs, it would be expected that those with a parent who attended IRS would be at an elevated risk for suicidal thoughts or attempts earlier in life, which could be a contributor to the differential rates of suicide evident in younger v .…”

Genetics Factors in Major Depression Disease

“…This design included a more rigorous approach to inclusion of samples and consideration of factors such as the patients' sex, clinical DD variation, clinical onset age, and other factors that can affect the risk of disease and its progression. However, these factors may exert no influence on the risk of DD development; for example, the clinical onset age was recently shown to not affect the association analysis results in the Chinese CONVERGE sample ( 127 ).…”

Immune to happiness – inflammatory process indicators and depressive personality traits

“…In the 1990s, monoamine theories seemed to be the gold standard, exploited by the pharmaceutical industry [3]. Over the years, however, they have proven to be insufficient and depression has become an increasingly common disease in all age groups [4,5].…”