期刊
BIOLOGICAL PSYCHIATRY
卷 64, 期 4, 页码 302-310出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2008.03.014
关键词
anxiety; association study; catechol-O-methyltransferase; depression; genetics; personality
资金
- NIAAA NIH HHS [MH/AA/DA-49492] Funding Source: Medline
- NIDA NIH HHS [R01 DA011287, DA-11287] Funding Source: Medline
- NIMH NIH HHS [MH-65322, K08 MH066277-05, R01 MH065322, T32 MH020030, MH-20030, K08 MH-66277, K08 MH066277, R01 MH040828] Funding Source: Medline
Background: Catechol-C-methyltransferase (COMT) has been investigated for its possible role in a wide range of psychiatric phenotypes. In particular, several studies support association of this gene with panic disorder and other anxiety-related traits. Methods: We examined the COMT gene for association with genetic risk across a range of anxiety spectrum phenotypes. We used multivariate structural equation modeling to select twin pairs scoring at the extremes of a latent genetic risk factor shared by neuroticism, several anxiety disorders, and major depression from a large population-based twin sample. With one member from each of these pairs, the resulting sample of 589 cases and 539 control subjects were entered into a two-stage association study in which genetic markers were screened in stage 1, the positive results of which were tested for replication in stage 2. Results: The functional val 158met polymorphism (rs4680) plus nine other single nucleotide polymorphism markers selected to capture the major allelic variation across the COMT locus were analyzed for differences between cases and control subjects. Although the val (G) allele of rs4680 showed marginally significant association in our combined stage I plus stage 2 sample, a high-risk haplotype of this allele with the A allele of rs165599 was significantly over-represented in cases (p = 1.97e-5, odds ratio = 1.95). This haplotype also predicted individual differences in neuroticism and risk for several anxiety disorders and major depression. Consistent with prior studies, our findings are female-specific. Conclusions: Variations in the COMT gene contribute to genetic risk shared across a range of anxiety-related phenotypes.
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