SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.
SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians.
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DOI：
10.1371/journal.pone.0058618
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kuwano R
中科院分区：
文献类型：
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作者：
Miyashita A;Koike A;Jun G;Wang LS;Takahashi S;Matsubara E;Kawarabayashi T;Shoji M;Tomita N;Arai H;Asada T;Harigaya Y;Ikeda M;Amari M;Hanyu H;Higuchi S;Ikeuchi T;Nishizawa M;Suga M;Kawase Y;Akatsu H;Kosaka K;Yamamoto T;Imagawa M;Hamaguchi T;Yamada M;Morihara T;Takeda M;Takao T;Nakata K;Fujisawa Y;Sasaki K;Watanabe K;Nakashima K;Urakami K;Ooya T;Takahashi M;Yuzuriha T;Serikawa K;Yoshimoto S;Nakagawa R;Kim JW;Ki CS;Won HH;Na DL;Seo SW;Mook-Jung I;Alzheimer Disease Genetics Consortium;St George-Hyslop P;Mayeux R;Haines JL;Pericak-Vance MA;Yoshida M;Nishida N;Tokunaga K;Yamamoto K;Tsuji S;Kanazawa I;Ihara Y;Schellenberg GD;Farrer LA;Kuwano R
为了发现晚发性阿尔茨海默病（LOAD）的易感基因，我们使用三个人群进行了3阶段全基因组关联研究（GWAS）：日本阿尔茨海默病遗传联盟（JGSCAD）的日本人，韩国人和阿尔茨海默病遗传联盟（ADGC）的高加索人。在第1阶段，我们评估了日本病例（n = 1，008）和对照（n = 1，016）中5，877，918个基因型和插补SNP的数据。 在APOE区域的12个SNP中观察到全基因组意义。在第二个日本样本（885例病例，985例对照）中，对来自其他不同地区的7个p值<2×10−5的SNP进行了基因分型，并证实了一个SORL 1 SNP（rs3781834，合并样本中P=7.33×10−7）的相关性证据。 随后的分析结合了日本人、韩国人（339例，1，129例对照）和高加索人（11，840例AD病例，10，931例对照）中几个SORL 1 SNP的结果，揭示了rs11218343（P = 1.77×10−9）和rs3781834（P = 1.04×10−8）的全基因组显著性。 先前在高加索人中建立的AD基因座中的SNP在日本人中显示出强有力的关联证据，包括PICALM附近的rs3851179（P = 1.71×10−5）和BIN1附近的rs744373（P = 1.39×10−4）。 这些SNPs的相关等位基因与高加索人相同。这些数据首次证明了LOAD与SORL 1的全基因组意义，并证实了其他已知基因座在日本LOAD中的作用。我们的研究强调了检查多种族人群中相关性的重要性。
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.
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DOI：
10.1186/alzrt26
发表时间：
2010-03-05
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Ertekin-Taner N
通讯作者：
Ertekin-Taner N
影响因子：
5.3
作者：
Fjorback, Anja W.;Seaman, Matthew;Andersen, Olav M.
通讯作者：
Andersen, Olav M.
DOI：
10.1073/pnas.0503689102
发表时间：
2005-09-20
影响因子：
11.1
作者：
Andersen, OM;Reiche, J;Willnow, TE
通讯作者：
Willnow, TE
影响因子：
11
作者：
Pottier, C.;Hannequin, D.;Campion, D.
通讯作者：
Campion, D.
影响因子：
30.8
作者：
通讯作者：
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