Identification of New Putative Susceptibility Genes for Several Psychiatric Disorders by Association Analysis of Regulatory and Non-Synonymous SNPs of 306 Genes Involved in Neurotransmission and Neurodevelopment
Identification of New Putative Susceptibility Genes for Several Psychiatric Disorders by Association Analysis of Regulatory and Non-Synonymous SNPs of 306 Genes Involved in Neurotransmission and Neurodevelopment
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DOI：
10.1002/ajmg.b.30902
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发表时间：
2009-09-05
影响因子：
2.8
通讯作者：
Carracedo, Angel
中科院分区：
文献类型：
--
作者：
Gratacos, Monica;Costas, Javier;Carracedo, Angel
人类遗传学研究中的一个基本难题是确定导致常见/复杂疾病易感性的基因变异谱。在此我们检验了功能性基因变异可能导致几种相关常见疾病易感性这一假设。我们分析了五种主要的精神疾病诊断类别（物质滥用、焦虑、进食、精神病和情绪障碍）以及两个不同的对照组，总共3214个样本，针对涉及神经传递和/或神经发育的306个基因的748个启动子和非同义单核苷酸多态性（SNP）进行了分析。我们发现了与个别疾病的强关联，例如生长激素释放激素（GHRH）与焦虑障碍，催乳素调节元件（PREB）与进食障碍，离子型红藻氨酸谷氨酸受体5（GRIK5）与双相障碍，以及几个与多种疾病相关的SNP，这些可能代表个体和相关疾病的易感性因素。值得注意的是，位于缓激肽受体B2基因（BDKRB2）启动子区域的一个功能性SNP，rs945032，与三种疾病（惊恐障碍、物质滥用和双相障碍）相关，另外两个BDKRB2的SNP与强迫症和重度抑郁症相关，为几种相关精神疾病的易感性常见变异提供了证据。BDKRB2（比值比在1.65到3.06之间）与几种精神疾病的关联支持了一种常见基因变异可能导致临床相关表型易感性的观点，并为精神疾病的病理生理学提供了一个新的功能性线索。（C）2008威利 - 利斯公司
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.