Laboratory for International Alliance, RIKEN Center for Genomic Medicine, Suehiro-cho, Tsurumi-ku, Yokohama, Japan.
Genes Brain Behav. 2011 Oct;10(7):789-97. doi: 10.1111/j.1601-183X.2011.00721.x. Epub 2011 Aug 18.
Bipolar disorder is a severe psychiatric disorder influenced by environmental and genetic factors. Genetic studies have implicated many variants in the disease's etiology but only few have been successfully replicated. We conducted a genome-wide association study (GWAS) on bipolar disorder in the Bulgarian population followed by a replication study of the top 100 single nucleotide polymorphisms (SNPs) showing the smallest P values. The GWAS was performed on 188 bipolar disorder patients and 376 control subjects genotyped on the Illumina 550 platform. The replication study was conducted on 122 patients and 328 controls. Although our study did not show any association P value that achieved genome-wide significance, and none of the top 100 SNPs reached the Bonferroni-corrected P value in the replication study, the plausible involvement of some variants cannot be entirely discarded. Three polymorphisms, rs8099939 [P = 2.12 × 10(-6), odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.43-2.67] in GRIK5, rs6122972 (P = 3.11 × 10(-6), OR = 2.02, 95% CI = 1.46-2.80) in PARD6B and rs2289700 (P = 9.14 × 10(-6), OR = 2.13, 95% CI = 1.53-2.95) in CTSH remained associated at a similar level after Mantel-Haenszel test for combining the results from the genome-wide and replication studies. A modest association was also detected for SNP rs1012053 (GWAS P = 4.50 × 10(-2)) in DGKH, which has already been reported as the most significant variant in a previous genome-wide scan on bipolar disorder. However, further studies using larger datasets are needed to identify variants with smaller effects that contribute to the risk of bipolar disorder.
双相情感障碍是一种严重的精神疾病，受到环境和遗传因素的影响。遗传研究已经发现了许多与该病发病机制相关的变异，但只有少数得到了成功复制。我们对保加利亚人群中的双相情感障碍进行了全基因组关联研究（GWAS），随后对显示最小 P 值的前 100 个单核苷酸多态性（SNP）进行了复制研究。GWAS 对 188 名双相情感障碍患者和 376 名经 Illumina 550 平台基因分型的对照进行了研究。复制研究在 122 名患者和 328 名对照中进行。尽管我们的研究没有显示任何达到全基因组显著性水平的关联 P 值，而且在复制研究中也没有前 100 个 SNP 达到 Bonferroni 校正的 P 值，但一些变体的合理参与也不能完全排除。三个多态性，rs8099939[P=2.12×10(-6)，优势比（OR）=1.95，95%置信区间（CI）=1.43-2.67]在 GRIK5，rs6122972[P=3.11×10(-6)，OR=2.02，95%置信区间（CI）=1.46-2.80]在 PARD6B 和 rs2289700[P=9.14×10(-6)，OR=2.13，95%置信区间（CI）=1.53-2.95]在 CTSH 在全基因组和复制研究结果的合并 Mantel-Haenszel 检验中保持相似水平的关联。在 DGKH 中，SNP rs1012053（GWAS P=4.50×10(-2)) 也检测到适度关联，该 SNP 已在先前的双相情感障碍全基因组扫描中被报道为最显著的变体。然而，需要使用更大的数据集进行进一步研究，以确定对双相情感障碍风险有较小影响的变体。
