title: 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.
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Akinori
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authors.forename: Kenji
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authors.lastname: Nakashima
authors.forename: Katsuya
authors.initials: K
authors.lastname: Urakami
authors.forename: Terumi
authors.initials: T
authors.lastname: Ooya
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takefumi
authors.initials: T
authors.lastname: Yuzuriha
authors.forename: Kayoko
authors.initials: K
authors.lastname: Serikawa
authors.forename: Seishi
authors.initials: S
authors.lastname: Yoshimoto
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakagawa
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.forename: Inhee
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authors.lastname: Mook-Jung
authors.forename: Peter
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authors.lastname: St George-Hyslop
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
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authors.lastname: Haines
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authors.lastname: Pericak-Vance
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authors.lastname: Yoshida
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ihara
authors.forename: Gerard D
authors.initials: GD
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mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D044465:White People / Q000235:genetics*
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human
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