Whole-genome association study of bipolar disorder
Whole-genome association study of bipolar disorder
复制标题
DOI：
10.1038/sj.mp.4002151
复制
发表时间：
2008-06-01
影响因子：
11
通讯作者：
Purcell, S. M.
中科院分区：
文献类型：
--
作者：
Sklar, P.;Smoller, J. W.;Purcell, S. M.
我们对1461例双相(BP)1障碍患者、2008名来自双相障碍系统治疗增强计划的对照和伦敦大学学院样本收集进行了全基因组关联扫描，成功地对372 193个单核苷酸多态(SNPs)进行了基因分型。我们最强的单一SNP结果是在肌球蛋白5B(MYO5B；P=1.66 x 10(-7))和TSPAN8(TSPAN8；P=6.11 x 10(-7))中。单倍型分析进一步支持MYO5B、TSPAN8和表皮生长因子受体(MYO5B；P=2.04×10(-8)，TSPAN8；P=7.57×10(-7)和EGFR；P=8.36×10(-8))的单一SNP结果。在复制方面，我们对家族性NIMH样本(n=409 Trio)和爱丁堡大学病例对照样本(n=365例，351例对照)中的304个SNPs进行了基因分型，这些样本在多次检测校正后没有提供独立的复制。我们与1,868名BP疾病患者和2,938名对照的全基因组扫描的最强相关性的比较表明，电压依赖性钙通道L型阿尔法1C亚单位(CACNA1C)基因内的SNPs信号一致。考虑到BP疾病的遗传性，研究之间的不一致强调了易感等位基因的影响很可能是适度的，需要更大的样本来检测。
We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P = 1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P = 6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P = 2.04 x 10(-8), TSPAN8; P = 7.57 x 10(-7) and EGFR; P = 8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n = 409 trios) and University of Edinburgh case-control samples (n = 365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.