Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
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DOI：
10.1016/j.jalz.2016.12.012
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Farrer LA
中科院分区：
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作者：
Jun GR;Chung J;Mez J;Barber R;Beecham GW;Bennett DA;Buxbaum JD;Byrd GS;Carrasquillo MM;Crane PK;Cruchaga C;De Jager P;Ertekin-Taner N;Evans D;Fallin MD;Foroud TM;Friedland RP;Goate AM;Graff-Radford NR;Hendrie H;Hall KS;Hamilton-Nelson KL;Inzelberg R;Kamboh MI;Kauwe JSK;Kukull WA;Kunkle BW;Kuwano R;Larson EB;Logue MW;Manly JJ;Martin ER;Montine TJ;Mukherjee S;Naj A;Reiman EM;Reitz C;Sherva R;St George-Hyslop PH;Thornton T;Younkin SG;Vardarajan BN;Wang LS;Wendlund JR;Winslow AR;Alzheimer's Disease Genetics Consortium;Haines J;Mayeux R;Pericak-Vance MA;Schellenberg G;Lunetta KL;Farrer LA
阿尔茨海默病（AD）的遗传位点已被确定在欧洲血统的白人，但在其他人群中AD的遗传结构是不太了解。我们进行了一项跨种族全基因组关联研究（GWAS）的迟发性AD的第一阶段的样本，包括白人的欧洲裔，非洲裔美国人，日本人和以色列阿拉伯人组装的阿尔茨海默病遗传学联盟（ADGC）。使用国际基因组学阿尔茨海默病项目（IGAP）GWAS数据集中的总结结果，对来自新基因座的第1阶段的提示性结果进行了随访。在基于SNP的检验中，PFDN 1/HBEGF、USP 6 NL/ECHDC 3和BZRAP 1-AS 1的SNP以及APOE ε4等位基因与NFIC SNP的相互作用均存在全基因组显著（GWS）关联（P<5×10−8）。我们还获得了GWS证据（P<2.7×10−6），证明总样本中基于基因的关联与一个新位点TPBG（P=1.8×10−6）有关。我们的研究结果强调了跨种族研究对识别新的AD易感基因的价值。
Genetic loci for Alzheimer disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer’s Disease Genetics Consortium (ADGC). Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer’s Project (IGAP) GWAS dataset. Genome-wide significant (GWS) associations in SNP-based tests (P<5×10−8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1, and for the interaction of the APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P<2.7×10−6) for gene-based association in the total sample with a novel locus, TPBG (P=1.8×10−6). Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.