Genetic Epidemiology of Major Depression: Review and Meta-Analysis

doi:10.1176/appi.ajp.157.10.1552



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	Depression
	Genetics
	Epidemiology

Am J Psychiatry 157:1552-1562, October 2000
© 2000 American Psychiatric Association

Reviews and Overviews

Genetic Epidemiology of Major Depression: Review and Meta-Analysis

Patrick F. Sullivan, M.D., F.R.A.N.Z.C.P., Michael C. Neale, Ph.D., and Kenneth S. Kendler, M.D.

Abstract

OBJECTIVE: The authors conducted a meta-analysis of relevantdata from primary studies of the genetic epidemiology of majordepression.METHOD: The authors searched MEDLINE and the referencelists of previous review articles to identify relevant primarystudies. On the basis of a review of family, adoption, and twinstudies that met specific inclusion criteria, the authors derivedquantitative summary statistics. RESULTS: Five family studiesmet the inclusion criteria. The odds ratios for proband (subjectswith major depression or comparison subjects) versus first-degreerelative status (affected or unaffected with major depression)were homogeneous across the five studies (Mantel-Haenszel oddsratio=2.84, 95% CI=2.31–3.49). No adoption study met theinclusion criteria, but the results of two of the three reportswere consistent with genetic influences on liability to majordepression. Five twin studies met the inclusion criteria, andtheir statistical summation suggested that familial aggregationwas due to additive genetic effects (point estimate of heritabilityof liability=37%, 95% CI=31%–42%), with a minimal contributionof environmental effects common to siblings (point estimate=0%,95% CI=0%–5%), and substantial individual-specific environmentaleffects/measurement error (point estimate=63%, 95% CI=58%–67%).The literature suggests that recurrence best predicts the familialaggregation of major depression. CONCLUSIONS: Major depressionis a familial disorder, and its familiality mostly or entirelyresults from genetic influences. Environmental influences specificto an individual are also etiologically significant. Major depressionis a complex disorder that does not result from either geneticor environmental influences alone but rather from both. Thesefindings are notably consistent across samples and methods andare likely to be generally applicable.

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