 |
|
Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of DepressionA Meta-analysis
Neil Risch, PhD;
Richard Herrell, PhD;
Thomas Lehner, PhD;
Kung-Yee Liang, PhD;
Lindon Eaves, PhD;
Josephine Hoh, PhD;
Andrea Griem, BS;
Maria Kovacs, PhD;
Jurg Ott, PhD;
Kathleen Ries Merikangas, PhD
JAMA. 2009;301(23):2462-2471.
Context 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.
Objective 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.
Data Sources Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis.
Study Selection 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,  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.
Data Extraction 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.
Results 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.
Conclusion 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.
Author Affiliations: Institute for Human Genetics, University of California at San Francisco, and Kaiser Permanente Northern California Division of Research, Oakland (Dr Risch); Genetic Epidemiology Research Branch, National Institute of Mental Health, Bethesda, Maryland (Drs Herrell, Lehner, and Merikangas and Ms Griem); Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland (Dr Liang); Departments of Human Genetics and Psychiatry, Virginia Commonwealth University, Richmond (Dr Eaves); Department of Epidemiology and Public Health, School of Medicine, Yale University, New Haven, Connecticut (Dr Hoh); Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Kovacs); and Laboratory of Statistical Genetics, Rockefeller University, New York, NY (Dr Ott).
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED LETTERS
Gene-Environment Interactions and Depression
Karestan C. Koenen and Sandro Galea
JAMA. 2009;302(17):1859-1862.
EXTRACT
| FULL TEXT
Gene-Environment Interactions and Depression
Francis E. Lotrich and Eric Lenze
JAMA. 2009;302(17):1859-1862.
EXTRACT
| FULL TEXT
Gene-Environment Interactions and Depression
Christian Schwahn and Hans Jörgen Grabe
JAMA. 2009;302(17):1859-1862.
EXTRACT
| FULL TEXT
Gene-Environment Interactions and Depression
Nina Rieckmann, Michael A. Rapp, and Jacqueline Müller-Nordhorn
JAMA. 2009;302(17):1859-1862.
EXTRACT
| FULL TEXT
Gene-Environment Interactions and Depression—Reply
Kathleen Ries Merikangas, Thomas Lehner, and Neil J. Risch
JAMA. 2009;302(17):1859-1862.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Gene-Environment Interactions and Depression
Koenen and Galea
JAMA 2009;302:1859-1862.
FULL TEXT
Gene-Environment Interactions and Depression
Lotrich and Lenze
JAMA 2009;302:1859-1862.
FULL TEXT
Gene-Environment Interactions and Depression
Schwahn and Grabe
JAMA 2009;302:1859-1862.
FULL TEXT
Gene-Environment Interactions and Depression
Rieckmann et al.
JAMA 2009;302:1859-1862.
FULL TEXT
Deciphering the Interaction of the Corticotropin-Releasing Factor and Serotonin Brain Systems in Anxiety-Related Disorders
Homberg and Contet
J. Neurosci. 2009;29:13743-13745.
FULL TEXT
Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene
Chiao and Blizinsky
Proc R Soc B 2009;0:rspb.2009.1650v1-rspb20091650.
ABSTRACT
| FULL TEXT
Culture, serotonin receptor polymorphism and locus of attention
Kim et al.
Soc Cogn Affect Neurosci 2009;0:nsp040v1-nsp040.
ABSTRACT
| FULL TEXT
Gene-Environment-Wide Interaction Studies in Psychiatry
van Os and Rutten
Am. J. Psychiatry 2009;166:964-966.
FULL TEXT
Debunking the Serotonin Gene-Life Stress Hypothesis?
JWatch Psychiatry 2009;2009:1-1.
FULL TEXT
Doubts About Genetic Determinants of Depression Risk
JWatch General 2009;2009:4-4.
FULL TEXT
|
