期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 150B, 期 6, 页码 808-816出版社
WILEY
DOI: 10.1002/ajmg.b.30902
关键词
candidate gene; SNP; molecular epidemiology; case-control studies
资金
- Ministry of Education and Science [SAF2005-01005]
- Fondo de Investigaciones Sanitarias dela Seguridad Social (FIS) [PI040632, PI040619]
- Department of Health and Department of Universities, Research and Information Society (Generalitat de Catalunya) [2005SGR00008, 2005SGR00322]
- EC [QLKI-1999-916]
- European Union [FP6 LSHMCT-2003-503041]
- Genome Spain to the National Genotyping Center (CeGen)
A fundamental difficulty in human genetics research is the identification of the spectrum of genetic variants that contribute to the susceptibility to common/complex disorders. We tested here the hypothesis that functional genetic variants may confer susceptibility to several related common disorders. We analyzed five main psychiatric diagnostic categories (substance-abuse, anxiety, eating, psychotic, and mood disorders) and two different control groups, representing a total of 3,214 samples, for 748 promoter and non-synonymous single nucleotide polymorphisms (SNPs) at 306 genes involved in neurotransmission and/or neurodevelopment. We identified strong associations to individual disorders, such as growth hormone releasing hormone (GHRH) with anxiety disorders, prolactin regulatory element (PREB) with eating disorders, ionotropic kainate glutamate receptor 5 (GRIK5) with bipolar disorder and several SNPs associated to several disorders, that may represent individual and related disease susceptibility factors. Remarkably, a functional SNP, rs945032, located in the promoter region of the bradykinin receptor B2 gene (BDKRB2) was associated to three disorders (panic disorder, substance abuse, and bipolar disorder), and two additional BDKRB2 SNPs to obsessive-compulsive disorder and major depression, providing evidence for common variants of susceptibility to several related psychiatric disorders. The association of BDKRB2 (odd ratios between 1.65 and 3.06) to several psychiatric disorders supports the view that a common genetic variant could confer susceptibility to clinically related phenotypes, and defines a new functional hint in the pathophysiology of psychiatric diseases. (C) 2008 Wiley-Liss, Inc.
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