跨种族全基因组扫描发现新的阿尔茨海默病基因座。
Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
作者信息
Jun Gyungah R, Chung Jaeyoon, Mez Jesse, Barber Robert, Beecham Gary W, Bennett David A, Buxbaum Joseph D, Byrd Goldie S, Carrasquillo Minerva M, Crane Paul K, Cruchaga Carlos, De Jager Philip, Ertekin-Taner Nilufer, Evans Denis, Fallin M Danielle, Foroud Tatiana M, Friedland Robert P, Goate Alison M, Graff-Radford Neill R, Hendrie Hugh, Hall Kathleen S, Hamilton-Nelson Kara L, Inzelberg Rivka, Kamboh M Ilyas, Kauwe John S K, Kukull Walter A, Kunkle Brian W, Kuwano Ryozo, Larson Eric B, Logue Mark W, Manly Jennifer J, Martin Eden R, Montine Thomas J, Mukherjee Shubhabrata, Naj Adam, Reiman Eric M, Reitz Christiane, Sherva Richard, St George-Hyslop Peter H, Thornton Timothy, Younkin Steven G, Vardarajan Badri N, Wang Li-San, Wendlund Jens R, Winslow Ashley R, Haines Jonathan, Mayeux Richard, Pericak-Vance Margaret A, Schellenberg Gerard, Lunetta Kathryn L, Farrer Lindsay A
机构信息
Neurogenetics and Integrated Genomics, Andover Innovative Medicines Institute, Eisai Inc, Andover, MA, USA; Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
出版信息
Alzheimers Dement. 2017 Jul;13(7):727-738. doi: 10.1016/j.jalz.2016.12.012. Epub 2017 Feb 7.
INTRODUCTION
Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood.
METHODS
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. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset.
RESULTS
Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10).
DISCUSSION
Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.
引言
阿尔茨海默病（AD）的基因位点已在欧洲血统的白人中得到确认，但其他人群中AD的遗传结构尚不清楚。
方法
我们在第1阶段样本中开展了一项跨种族全基因组关联研究（GWAS），用于晚发性AD，该样本包括由阿尔茨海默病遗传学联盟汇集的欧洲血统白人、非裔美国人、日本人及以色列阿拉伯人。利用国际基因组学阿尔茨海默病项目GWAS数据集中的汇总结果，对第1阶段来自新位点的提示性结果进行了后续研究。
结果
在基于单核苷酸多态性（SNP）的检测中（P < 5×10），确定了PFDN1/HBEGF、USP6NL/ECHDC3和BZRAP1-AS1中的SNP以及（载脂蛋白E）APOE ε4等位基因与NFIC SNP之间的相互作用具有全基因组显著性（GWS）关联。我们还在总样本中获得了基于基因关联的GWS证据（P < 2.7×10），该关联涉及一个新位点TPBG（P = 1.8×10）。
讨论
我们的研究结果突出了跨种族研究在识别新的AD易感位点方面的价值。
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