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基于 II 型糖尿病 GWAS 的检测风险变异与日本人群精神障碍的遗传关联研究。

Genetic association study between the detected risk variants based upon type II diabetes GWAS and psychotic disorders in the Japanese population.

机构信息

Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan.

Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.

出版信息

J Hum Genet. 2014 Jan;59(1):54-6. doi: 10.1038/jhg.2013.116. Epub 2013 Nov 7.

Abstract

Several epidemiological and genetic studies have suggested that the risk of type II diabetes (T2D) is likely to overlap with the susceptibility to psychotic disorders such as schizophrenia (SCZ) and bipolar disorder (BD). In this study, we aimed to examine the association of single-nucleotide polymorphisms (SNPs) detected in previous T2D genome-wide association studies (GWAS) with SCZ, BD and psychosis (SCZ plus BD). A total of 37 SNPs were selected from the literature. A two-stage analysis was conducted using a first set of screening samples (total N=3037) and a second set of replication samples (N=4950). None of the SNPs showed a significant association to the screening samples after correction for multiple testing. To avoid type II error, we genotyped the top three SNPs in BCL11A, HMG20A and HNF4A showing associations with any of the phenotypes (Puncorrected <0.01) using independent samples to replicate the nominal associations. However, we were unable to find any significant associations based on the screening results (Puncorrected>0.05). Our findings did not support the shared genetic risk between T2D and psychotic disorders in the Japanese population. However, further replication using a larger sample size is required.

摘要

几项流行病学和遗传学研究表明,2 型糖尿病(T2D)的风险很可能与精神障碍(如精神分裂症(SCZ)和双相情感障碍(BD))的易感性重叠。在这项研究中,我们旨在研究先前 T2D 全基因组关联研究(GWAS)中检测到的单核苷酸多态性(SNP)与 SCZ、BD 和精神病(SCZ+BD)之间的关联。从文献中选择了 37 个 SNP。使用第一组筛选样本(总 N=3037)和第二组复制样本(N=4950)进行两阶段分析。在进行多次测试校正后,没有 SNP 与筛选样本显示出显著关联。为了避免第二类错误,我们使用独立样本对与任何表型相关联(未校正的 P<0.01)的 BCL11A、HMG20A 和 HNF4A 中显示出关联的三个 SNP 进行了基因分型,以复制名义关联。然而,根据筛选结果,我们没有发现任何显著的关联(未校正的 P>0.05)。我们的研究结果不支持日本人群中 T2D 和精神障碍之间存在共同的遗传风险。然而,需要使用更大的样本量进行进一步的复制。

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