Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.
Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.
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主要的情绪障碍，包括双相情感障碍(BD)和严重抑郁障碍(MDD)，基本上是可遗传的，但几乎没有危险基因被确定。我们对5个主要的心境障碍病例对照样本进行了荟萃分析，其中包括超过13,600个独特的个体，这些个体在高密度阵列上具有大约500,000到100万个单核苷酸多态(SNP)标记。等位基因关联结果用样本大小加权的方法进行荟萃分析。我们发现了全基因组的重要证据，即染色体3p21.1区域的SNPs与主要的情绪障碍有关。SNP rs2251219返回的荟萃分析p值最小，为3.63×10−8，合并优势比为0.87.在重复研究中测试的3个独立样本中，有2个观察到了支持性结果。这些结果表明，该区域的一个或多个基因与主要情绪障碍的病因有关，并表明BD和MDD具有共同的遗传风险因素。
The major mood disorders, which include bipolar disorder (BD) and major depressive disorder (MDD), are substantially heritable, but few risk loci have been identified. We performed a meta-analysis of 5 major mood disorder case-control samples, including over 13,600 unique individuals genotyped with approximately 500,000 to 1 million single nucleotide polymorphism (SNP) markers on high-density arrays. Allele-wise association results were meta-analyzed with a method that weights results by sample size. We found genome-wide significant evidence that SNPs in a region of chromosome 3p21.1were associated with major mood disorders. The SNP rs2251219 returned the smallest meta-analysis p-value, 3.63 × 10−8, with a pooled odds ratio of 0.87. Supportive results were observed in 2 out of 3 independent samples tested in a replication study. These results implicate one or more genes in this region in the etiology of major mood disorders and suggest that BD and MDD share genetic risk factors.