Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis.
Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis.
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DOI：
10.1038/mp.2017.154
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发表时间：
2018-05
影响因子：
11
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
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文献类型：
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作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
两个强迫症全基因组关联研究（GWAS）已经由独立的强迫症联盟，国际强迫症基金会遗传学协作（IOCDF-GC）和强迫症协作遗传学关联研究（OCGAS）发表，但许多排名靠前的信号仅在一项研究中得到支持。因此，我们对这两个联盟进行了荟萃分析，共调查了2，688名欧洲血统的强迫症患者和7，037名基因组匹配的对照。没有SNP达到全基因组显著性。然而，与两个单独的GWAS相比，p值的分布向显著性方向移动。顶部单倍型区块标记为rs 4733767（p=7.1×10−7; OR=1.21;（CI：1.12，1.31）; CASC 8/CASC 11）、rs 1030757（p=1.1×10−6; OR=1.18;CI：1.10，1.26，GRID 2）和rs 12504244（p=1.6×10−6; OR=1.18;CI：1.11，1.27，KIT）。位于基因ASB 13、RSPO 4、DLGAP 1、PTPRD、GRIK 2、FAIM 2和CDH 20中或附近的变异体，在连锁峰和原始GWAS中鉴定，属于最高信号。每项研究的多基因风险评分分别解释了OCGAS和欧洲IOCDF-GC目标样本中0.9%（p=0.003）和0.3%（p=0.0009）的表型方差，从而预测了另一项研究的病例/对照状态。OCGAS和IOCDF-GC组合样本中常见的SNP遗传力估计为0.28（s.e. = 0.04）。值得注意的是，在OCGAS样本中，约65%的SNP遗传力是由次要等位基因频率等于或大于40%的SNP所解释的。这项联合分析构成了迄今为止最大的单次OCD全基因组研究，代表了阐明OCD遗传原因的重要综合步骤。
Two OCD genome-wide association studies (GWAS) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2,688 individuals of European ancestry with OCD, and 7,037 genomically matched controls. No SNPs reached genome-wide significance. However, in comparison to the two individual GWASs, the distribution of p-values shifted towards significance. The top haplotypic blocks were tagged with rs4733767 (p=7.1×10−7; OR=1.21;(CI: 1.12,1.31); CASC8/CASC11), rs1030757 (p=1.1×10−6; OR=1.18;CI:1.10,1.26, GRID2) and rs12504244 (p=1.6×10−6; OR=1.18;CI: 1.11,1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2, and CDH20, identified in linkage peaks and the original GWASs, were amongst the top signals. Polygenic risk scores for each individual study predicted case/control status in the other by explaining 0.9% (p=0.003) and 0.3% (p=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e. = 0.04). Strikingly, approximately 65% of the SNP based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies equal to or greater than 40%.This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.
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影响因子：
25
作者：
Malik, Athar N.;Vierbuchen, Thomas;Hemberg, Martin;Rubin, Alex A.;Ling, Emi;Couch, Cameron H.;Stroud, Hume;Spiegel, Ivo;Farh, Kyle Kai-How;Harmin, David A.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
--
作者：
Hudziak, JJ;van Beijsterveldt, CEM;Boomsma, DI
通讯作者：
Boomsma, DI
影响因子：
6.5
作者：
Kawakami, T;Soma, Y;Mizoguchi, M
通讯作者：
Mizoguchi, M
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium