一项针对日本人群迟发性阿尔茨海默病的全基因组关联研究。
A genome-wide association study of late-onset Alzheimer's disease in a Japanese population.
作者信息
Hirano Atsushi, Ohara Tomoyuki, Takahashi Atsushi, Aoki Masayuki, Fuyuno Yuta, Ashikawa Kyota, Morihara Takashi, Takeda Masatoshi, Kamino Kouzin, Oshima Etsuko, Okahisa Yuko, Shibata Nobuto, Arai Heii, Akatsu Hiroyasu, Ikeda Masashi, Iwata Nakao, Ninomiya Toshiharu, Monji Akira, Kitazono Takanari, Kiyohara Yutaka, Kubo Michiaki, Kanba Shigenobu
机构信息
aLaboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama bDepartment of Medicine and Clinical Science cDepartment of Neuropsychiatry dDepartment of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka eDepartment of Psychiatry, Osaka University Graduate School of Medicine, Osaka fNational Hospital Organization Yamato Mental Medical Center, Nara gDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama hDepartment of Psychiatry, Juntendo University School of Medicine, Tokyo iChoju Medical Institute, Fukushimura Hospital jDepartment of Psychiatry, Fujita Health University School of Medicine, Aichi kDepartment of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan.
出版信息
Psychiatr Genet. 2015 Aug;25(4):139-46. doi: 10.1097/YPG.0000000000000090.
OBJECTIVE
Although a number of genome-wide association studies (GWASs) of late-onset Alzheimer's disease (LOAD) have been carried out, there have been little GWAS data on East Asian populations.
DESIGN
To discover the novel susceptibility loci of LOAD, we carried out a GWAS using 816 LOAD cases and 7992 controls with a replication analysis using an independent panel of 1011 LOAD cases and 7212 controls in a Japanese population. In addition, we carried out a stratified analysis by APOE-ε4 status to eliminate the established effect of APOE region.
RESULTS
Our data indicated that 18p11.32 (rs1992269, P = 9.77 × 10(-7)), CNTNAP2 (rs802571, P = 1.26 × 10(-6)), and 12q24.23 (rs11613092, P = 6.85 × 10(-6)) were suggestive loci for susceptibility to LOAD.
CONCLUSION
We identified three suggestive loci for susceptibility to LOAD in a Japanese population. Among these, rs802571, located at intron 1 of CNTNAP2, was considered to be a plausible candidate locus from a functional perspective.
目的
尽管已经开展了多项晚发型阿尔茨海默病（LOAD）的全基因组关联研究（GWAS），但关于东亚人群的GWAS数据却很少。
设计
为了发现LOAD的新易感基因座，我们对816例LOAD病例和7992例对照进行了GWAS，并在日本人群中使用由1011例LOAD病例和7212例对照组成的独立样本进行了重复分析。此外，我们按APOE-ε4状态进行了分层分析，以消除APOE区域的既定效应。
结果
我们的数据表明，18p11.32（rs1992269，P = 9.77×10⁻⁷）、接触蛋白相关蛋白2（CNTNAP2，rs802571，P = 1.26×10⁻⁶）和12q24.23（rs11613092，P = 6.85×10⁻⁶）是LOAD易感性的提示性基因座。
结论
我们在日本人群中鉴定出了三个LOAD易感性的提示性基因座。其中，位于CNTNAP2内含子1的rs802571从功能角度来看被认为是一个合理的候选基因座。
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