Genetic epidemiology of major depression: Review and meta-analysis

Objective: The authors conducted a meta-analysis of relevant data from prim ary studies of the genetic epidemiology of major depression. Method: The authors searched MEDLINE and the reference lists of previous re view articles to identify relevant primary studies. On the basis of a revie w of Family, adoption, and twin studies that met specific inclusion criteri a, the authors derived quantitative summary statistics. Results: Five family studies met the inclusion criteria. The odds ratios fo r proband (subjects with major depression or comparison subjects) versus fi rst-degree relative status (affected or unaffected with major depression) w ere homogeneous across the five studies (Mantel-Haenszel odds ratio=2.84, 9 5% Cl=2.31-3.49). No adoption study met the inclusion criteria, but the res ults of two of the three reports were consistent with genetic influences on liability to major depression. Five twin studies met the inclusion criteri a, and their statistical summation suggested that familial aggregation was due to additive genetic effects (point estimate of heritability of liabilit y=37%, 95% Cl=31%-42%), with a minimal contribution of environmental effect s common to siblings (point estimate=0%, 95% Cl=0%-5%), and substantial ind ividual-specific environmental effects/measurement error (point estimate=63 %, 95% Cl=58%-67%). The literature suggests that recurrence best predicts t he familial aggregation of major depression. Conclusions: Major depression is a familial disorder, and its familiality m ostly or entirely results from genetic influences. Environmental influences specific to an individual are also etiologically significant. Major depres sion is a complex disorder that does not result from either genetic or envi ronmental influences alone but rather from both. These findings are notably consistent across samples and methods and are likely to be generally appli cable.