Genome-wide association study reveals two new risk loci for bipolar disorder
Genome-wide association study reveals two new risk loci for bipolar disorder
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DOI：
10.1038/ncomms4339
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发表时间：
2014-03-01
影响因子：
16.6
通讯作者：
Cichon, Sven
中科院分区：
文献类型：
--
作者：
Muehleisen, Thomas W.;Leber, Markus;Cichon, Sven
双相情感障碍（BD）是一种常见的高度遗传性精神疾病，全基因组关联研究（GWAS）已经有力地确定了涉及疾病病因的第一个常见遗传变异。这些数据还提供了强有力的证据，表明存在多个额外的风险位点，每个位点对BD易感性的影响相对较小。大样本是必要的，以检测这些风险位点。在这里，我们通过调查24，025名患者和对照样本中的230万个单核苷酸多态性（SNP），展示了迄今为止最大的BD GWAS的结果。我们在5个染色体区域检测到56个全基因组显著的SNP，包括先前报道的风险位点ANK3，ODZ4和TRANK 1，以及风险位点ADCY2（5p15.31）和MIR2113和POU3F2之间的区域（6q16.1）。ADCY2是cAMP信号传导中的关键酶，我们的发现为BD发展中涉及的生物学机制提供了新的见解。
Bipolar disorder (BD) is a common and highly heritable mental illness and genome-wide association studies (GWAS) have robustly identified the first common genetic variants involved in disease aetiology. The data also provide strong evidence for the presence of multiple additional risk loci, each contributing a relatively small effect to BD susceptibility. Large samples are necessary to detect these risk loci. Here we present results from the largest BD GWAS to date by investigating 2.3 million single-nucleotide polymorphisms (SNPs) in a sample of 24,025 patients and controls. We detect 56 genome-wide significant SNPs in five chromosomal regions including previously reported risk loci ANK3, ODZ4 and TRANK1, as well as the risk locus ADCY2 (5p15.31) and a region between MIR2113 and POU3F2 (6q16.1). ADCY2 is a key enzyme in cAMP signalling and our finding provides new insights into the biological mechanisms involved in the development of BD.