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SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.


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.

SUBMITTER: Miyashita A 

PROVIDER: S-EPMC3614978 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.

Miyashita Akinori A   Koike Asako A   Jun Gyungah G   Wang Li-San LS   Takahashi Satoshi S   Matsubara Etsuro E   Kawarabayashi Takeshi T   Shoji Mikio M   Tomita Naoki N   Arai Hiroyuki H   Asada Takashi T   Harigaya Yasuo Y   Ikeda Masaki M   Amari Masakuni M   Hanyu Haruo H   Higuchi Susumu S   Ikeuchi Takeshi T   Nishizawa Masatoyo M   Suga Masaichi M   Kawase Yasuhiro Y   Akatsu Hiroyasu H   Kosaka Kenji K   Yamamoto Takayuki T   Imagawa Masaki M   Hamaguchi Tsuyoshi T   Yamada Masahito M   Morihara Takashi T   Takeda Masatoshi M   Takao Takeo T   Nakata Kenji K   Fujisawa Yoshikatsu Y   Sasaki Ken K   Watanabe Ken K   Nakashima Kenji K   Urakami Katsuya K   Ooya Terumi T   Takahashi Mitsuo M   Yuzuriha Takefumi T   Serikawa Kayoko K   Yoshimoto Seishi S   Nakagawa Ryuji R   Kim Jong-Won JW   Ki Chang-Seok CS   Won Hong-Hee HH   Na Duk L DL   Seo Sang Won SW   Mook-Jung Inhee I   St George-Hyslop Peter P   Mayeux Richard R   Haines Jonathan L JL   Pericak-Vance Margaret A MA   Yoshida Makiko M   Nishida Nao N   Tokunaga Katsushi K   Yamamoto Ken K   Tsuji Shoji S   Kanazawa Ichiro I   Ihara Yasuo Y   Schellenberg Gerard D GD   Farrer Lindsay A LA   Kuwano Ryozo R  

PloS one 20130402 4


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  ...[more]

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