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Meta-analysis of genome-wide association studies for panic disorder in the Japanese population

机译:对日本人群恐慌症的全基因组关联研究的荟萃分析

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Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10?5, odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10?4). Polygenic scores calculated from weakly associated SNPs (PP. ? 2012 Macmillan Publishers Limited
机译:恐慌症(PD)是一种中度遗传性焦虑症,其发病机理尚不清楚。由于先前的关联研究缺乏能力,因此可能无法检测到与PD真正关联的基因。在这项研究中,我们使用Affymetrix Mapping 500K阵列或Genome-Wide Human SNP Array 6.0在两个独立的数据集中进行了全基因组关联研究(GWAS)。我们获得了每个GWAS的估算基因型,并对两个GWAS数据集(718例病例和1717例对照)进行了荟萃分析。为了进行随访,在329例病例和861例对照中测试了12个单核苷酸多态性(SNP)。使用GWAS或荟萃分析结果进行基因本体富集和候选基因分析。我们还将多基因评分分析应用于我们的两个GWAS样本,以检验有助于PD的多基因成分的假设。尽管在GWAS和荟萃分析中均未检测到全基因组显着的SNP,但在多个基因座(如BDKRB2)中观察到提示性关联(P = 1.3×10 ?5 ,优势比= 1.31 )。在先前的候选基因中,获得了NPY5R与PD关联的支持证据(基因校正的P = 6.4×10 ?4 )。根据弱关联SNP计算的多基因得分(PP。?2012 Macmillan Publishers Limited

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