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在日本人群中,与体重指数相关的单核苷酸多态性与精神疾病和记忆表现的关联。

Association of body mass index-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population.

机构信息

1Department of Mental Disorder Research,National Center of Neurology and Psychiatry,National Institute of Neuroscience,Tokyo,Japan.

4Department of Psychiatry,National Center of Neurology and Psychiatry Hospital,Tokyo,Japan.

出版信息

Acta Neuropsychiatr. 2017 Oct;29(5):299-308. doi: 10.1017/neu.2016.66. Epub 2016 Dec 7.

Abstract

OBJECTIVE

Obesity is a risk factor for psychiatric diseases. Recently, a number of single nucleotide polymorphisms (SNPs) have been shown to be related to body mass index (BMI). In this study, we investigated the association of BMI-related SNPs with psychiatric diseases and one of their endophenotypes, memory performance, in a Japanese population.

METHODS

The subjects were 1624 patients with one of three psychiatric diseases (799 patients with major depressive disorder, 594 with schizophrenia, and 231 with bipolar disorder) and 1189 healthy controls. Memory performance was assessed using the Wechsler Memory Scale - Revised (WMS-R). Genomic DNA was prepared from venous blood and used to genotype 23 BMI-related SNPs using the TaqMan 5'-exonuclease allelic discrimination assay. We then analysed the relationships between the SNPs and psychiatric disease and various subscales of the WMS-R.

RESULTS

Three SNPs (rs11142387, rs12597579, and rs6548238) showed significant differences in the genotype or allele frequency between patients with any psychiatric diseases and controls. Furthermore, six SNPs (rs11142387, rs12597579, rs2815752, rs2074356, rs4776970, and rs2287019) showed significant differences in at least one subscale of the WMS-R depending on the genotypes of the healthy controls. Interestingly, rs11142387 near the Kruppel-like factor 9 (KLF9) was significantly associated with psychiatric disease and poor memory function.

CONCLUSIONS

We identified three and six BMI-related SNPs associated with psychiatric disease and memory performance, respectively. In particular, carrying the A allele of rs11142387 near KLF9 was found to be associated with psychiatric disease and poor memory performance, which warrants further investigations.

摘要

目的

肥胖是精神疾病的一个风险因素。最近,许多单核苷酸多态性(SNP)已被证明与体重指数(BMI)有关。在这项研究中,我们在日本人群中调查了与 BMI 相关的 SNP 与精神疾病及其一个表型特征,即记忆表现之间的关联。

方法

研究对象为 1624 名患有三种精神疾病之一的患者(799 名患有重度抑郁症、594 名患有精神分裂症和 231 名患有双相情感障碍)和 1189 名健康对照者。使用韦氏记忆量表修订版(WMS-R)评估记忆表现。从静脉血中提取基因组 DNA,并使用 TaqMan 5'-exonuclease 等位基因鉴别测定法对 23 个 BMI 相关 SNP 进行基因分型。然后,我们分析了 SNP 与精神疾病和 WMS-R 的各个分量表之间的关系。

结果

在患有任何精神疾病的患者和对照组之间,三个 SNP(rs11142387、rs12597579 和 rs6548238)在基因型或等位基因频率方面存在显著差异。此外,六个 SNP(rs11142387、rs12597579、rs2815752、rs2074356、rs4776970 和 rs2287019)根据健康对照者的基因型,在 WMS-R 的至少一个分量表中存在显著差异。有趣的是,位于 Kruppel 样因子 9(KLF9)附近的 rs11142387 与精神疾病和较差的记忆功能显著相关。

结论

我们确定了三个与精神疾病相关的 BMI 相关 SNP 和六个与记忆表现相关的 SNP。特别是,KLF9 附近 rs11142387 的 A 等位基因与精神疾病和较差的记忆表现相关,这值得进一步研究。

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