Familiality and SNP heritability of age at onset and episodicity in major depressive disorder

摘要: BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) recurrence/episodicity. Yet, evidence whether these subphenotypes are familial or heritable is scarce. The aims this study investigate the familiality AAO episode frequency in MDD assess proportion their variance explained by common single nucleotide polymorphisms (SNP heritability). METHOD: For investigating familiality, we used 691 families with 2-5 full siblings recurrent from DeNt study. We fitted (square root) count a linear negative binomial mixed model, respectively, family random effect adjusting for sex, center. strength was assessed intraclass correlation coefficients (ICC). For estimating SNP heritabilities, 3468 unrelated cases RADIANT GSK Munich studies. After similarly covariates, derived residuals were GREML method GCTA (genome-wide complex trait analysis) software. RESULTS: Significant clustering found both (ICC = 0.28) episodicity 0.07). calculated respective ICC estimates maximal additive heritability (0.56) (0.15). 0.17 (p 0.04); analysis underpowered calculating episodicity. CONCLUSIONS: AAO aggregate moderate small degree, respectively. under stronger control than episodicity. Larger samples needed calculate described statistical framework could be useful future analyses. KEYWORDS: major depression