我们进行了全基因组关联研究(GWAS)和双相情感障碍(BD)的随访研究,一种常见的神经精神疾病.在GWAS中,我们调查了682例BD患者和1300例对照患者的499,494个常染色体和12,484个X染色体SNP.在第一个后续步骤中,我们在1729例BD患者和2313例对照中检测了最显著的48个SNP.8个SNP显示出与BD的名义上显著的关联,并被引入GWAS的荟萃分析和首次随访样本。在2411例患者和3613例对照中,神经聚糖基因(NCAN)的遗传变异与BD的全基因组显着相关(rs1064395,p=3.02×10(-8);比值比=1.31)。在第二个后续步骤中,我们在BD的独立样本中复制了这一发现,总计6030名患者和31,749名对照(p=2.74×10(-4);比值比=1.12)。所有研究样本的组合分析得出的p值为2.14×10(-9)(比值比=1.17)。我们的结果提供了证据,表明rs1064395是BD的常见危险因素。NCAN编码神经聚糖,一种细胞外基质糖蛋白,这被认为与细胞粘附和迁移有关。我们发现小鼠中的表达位于皮质和海马区域内。这些领域涉及认知和情绪调节,并且先前已通过神经心理学与BD有关,神经影像学,和验尸研究。
We conducted a genome-wide association
study (GWAS) and a follow-up
study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the
neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10(-8); odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10(-4); odds ratio = 1.12). The combined analysis of all
study samples yielded a p value of 2.14 × 10(-9) (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes
neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.