Association study between the serotonin 1A receptor (HTR1A) gene and neuroticism, major depression, and anxiety disorders.

Abstract

The serotonin neurotransmitter system in general, and the serotonin 1A receptor in particular, has been broadly implicated in the pathophysiology of mood and anxiety disorders, although the results of genetic association studies have been mixed. In this study, we examined the serotonin 1A receptor gene, HTR1A, for its association with shared genetic risk across a range of anxiety and depression-related phenotypes. Using multivariate structural equation modeling, we selected twin pairs from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders scoring at the extremes of a latent genetic risk factor that underlies susceptibility to neuroticism, major depression, and several anxiety disorders. One member from each selected pair was entered into a 2-stage, case-control association study for the HTR1A gene. In the resulting sample of 589 cases and 539 controls, four SNPs spanning the HTR1A locus, including the C(-1019)G functional promoter polymorphism (rs6295), were screened in stage 1, the positive results of which were tested for replication in stage 2. While one marker met threshold significance criteria in stage 1, this association was not replicated in stage 2. Post-hoc analyses did not reveal association to any of the specific psychiatric phenotypes. Our data suggests that the HTR1A gene may not play a major role in the genetic susceptibility underlying depressive and anxiety-related phenotypes.

• Authors: J M Hettema, S S An, E J C G van den Oord, M C Neale, K S Kendler, X Chen
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 147B Issue 5 Pg. 661-6 (Jul 05 2008) ISSN: 1552-485X [Electronic] United States
• PMID: 18163385 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Twin Study)
• Copyright: Copyright 2007 Wiley-Liss, Inc.

Chemical References

• Receptor, Serotonin, 5-HT1A

Topics

• Adult
• Anxiety Disorders (genetics, metabolism)
• Depressive Disorder, Major (genetics, metabolism)
• Diseases in Twins (genetics, metabolism)
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Humans
• Linkage Disequilibrium
• Neurotic Disorders (genetics, metabolism)
• Receptor, Serotonin, 5-HT1A (genetics)