Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.
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DOI：
10.1038/mp.2012.73
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发表时间：
2012-09
影响因子：
11
通讯作者：
Sullivan, P. F.
中科院分区：
文献类型：
--
作者：
Bergen, S. E.;O'Dushlaine, C. T.;Ripke, S.;Lee, P. H.;Ruderfer, D. M.;Akterin, S.;Moran, J. L.;Chambert, K. D.;Handsaker, R. E.;Backlund, L.;Osby, U.;McCarroll, S.;Landen, M.;Scolnick, E. M.;Magnusson, P. K. E.;Lichtenstein, P.;Hultman, C. M.;Purcell, S. M.;Sklar, P.;Sullivan, P. F.
关键词：
精神分裂症(SCZ)和双相情感障碍(BD)是高度遗传的精神疾病，具有重叠的易感基因和症状。我们在瑞典的一个大样本中对这些疾病进行了全基因组关联研究。我们报告了一项新的独立病例对照分析，包括1507例SCZ病例、836例BD病例和2093例对照。在这些新样本中没有发现单核苷酸多态(SNP)；然而，结合新的和以前报道的SCZ样本(2111个SCZ和2535个对照)，发现主要组织相容性复合体(MHC)区域在全基因组范围内存在显著关联(rs886424，P=4.54×10−8)。使用多个参考小组和与精神病学基因组学联盟SCZ的荟萃分析的结果表明，在整个SCZ样本中，MHC区域存在广泛而显著的关联。我们评估了拷贝数变异(CNV)在这些受试者中的作用。与以前的报告一样，与对照组相比，SCZ中的缺失丰富，但BD病例中没有。单核苷酸缺失在两组病例中均高于对照组(SCZ：P=0.003，BD：P=0.013)，而最大CNV(>；500kb)仅在SCZ病例中显著丰富(P=0.0035)。两个具有SCZ关联的CNV在此SCZ样本中也被过度表达：16p11.2重复(P=0.0035)和22q11缺失(P=0.03)。这些结果强化了先前关于SCZ中存在显著的MHC和CNV相关性的报道，而不是BD。
Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case–control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P = 4.54 × 10−8). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P = 0.003, BD: P = 0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P = 0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P = 0.0035) and 22q11 deletions (P = 0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD.
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通讯作者：
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