NDLI: SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

Content Provider	PubMed Central
Author	Miyashita, Akinori Koike, Asako Jun, Gyungah Wang, Li-san Takahashi, Satoshi Matsubara, Etsuro Kawarabayashi, Takeshi Shoji, Mikio Tomita, Naoki Arai, Hiroyuki Asada, Takashi Harigaya, Yasuo Ikeda, Masaki Amari, Masakuni Hanyu, Haruo Higuchi, Susumu Ikeuchi, Takeshi Nishizawa, Masatoyo Suga, Masaichi Kawase, Yasuhiro Akatsu, Hiroyasu Kosaka, Kenji Yamamoto, Takayuki Imagawa, Masaki Hamaguchi, Tsuyoshi Yamada, Masahito Moriaha, Takashi Takeda, Masatoshi Takao, Takeo Nakata, Kenji Fujisawa, Yoshikatsu Sasaki, Ken Watanabe, Ken Nakashima, Kenji Urakami, Katsuya Ooya, Terumi Takahashi, Mitsuo Yuzuriha, Takefumi Serikawa, Kayoko Yoshimoto, Seishi Nakagawa, Ryuji Kim, Jong-won Ki, Chang-seok Won, Hong-hee Na, Duk L. Seo, Sang Won Mook-jung, Inhee Peter, St George-hyslop Mayeux, Richard Haines, Jonathan L. Pericak-vance, Margaret A. Yoshida, Makiko Nishida, Nao Tokunaga, Katsushi Yamamoto, Ken Tsuji, Shoji Kanazawa, Ichiro Ihara, Yasuo Schellenberg, Gerard D. Farrer, Lindsay A. Kuwano, Ryozo
Editor	Toft, Mathias
Copyright Year	2013
Abstract	To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values <2×10−5 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P = 7.33×10−7 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P = 1.77×10−9) and rs3781834 (P = 1.04×10−8). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P = 1.71×10−5) and rs744373 near BIN1 (P = 1.39×10−4). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations.
Related Links	http://dx.doi.org/10.1371/journal.pone.0058618
Starting Page	58618
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-04-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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