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PMID: 19531786 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.

JAMA ·Vol. 301 ·No. 23 ·2009-06-17 ·Pages 2462-71

Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR

Abstract

Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, > or = 3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14,250 participants, 1769 were classified as having depression; 12,481 as not having depression. In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.

MeSH Terms
Depressive Disorder, Major/genetics Female Genotype Humans Life Change Events Male Risk Factors Serotonin Plasma Membrane Transport Proteins/genetics Stress, Psychological/genetics
Chemicals
SLC6A4 protein, human Serotonin Plasma Membrane Transport Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Risch Neil
Institute for Human Genetics, University of California at San Francisco, and Kaiser Permanente Northern California Division of Research, Oakland, USA.
Herrell Richard
Lehner Thomas
Liang Kung-Yee
Eaves Lindon
Hoh Josephine
Griem Andrea
Kovacs Maria
Ott Jurg
Merikangas Kathleen Ries
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Article Info
Journal
JAMA
Abbr.
JAMA
ISSN
1538-3598
DOI
10.1001/jama.2009.878
Published
2009-06-17
Pages
2462-71
Language
English
Region
United States
NLM ID
7501160
PMCID
PMC2938776
Subset
IM
Grants
NCATS NIH HHS · UL1 TR000005 · United States
Intramural NIH HHS · Z01 MH002804-05 · United States
Corrections
ErratumIn
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CommentIn
PMID: 19887659
CommentIn
PMID: 19887660
CommentIn
PMID: 19887661
CommentIn
PMID: 19887662
CommentIn
PMID: 19996033
External Links
PubMed source DOI: 10.1001/jama.2009.878 PMC Full Text View journal details
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