两种罕见的AKAP9变异体与非裔美国人的阿尔茨海默病相关。
Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans.
作者信息
Logue Mark W, Schu Matthew, Vardarajan Badri N, Farrell John, Bennett David A, Buxbaum Joseph D, Byrd Goldie S, Ertekin-Taner Nilufer, Evans Denis, Foroud Tatiana, Goate Alison, Graff-Radford Neill R, Kamboh M Ilyas, Kukull Walter A, Manly Jennifer J
机构信息
Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
出版信息
Alzheimers Dement. 2014 Nov;10(6):609-618.e11. doi: 10.1016/j.jalz.2014.06.010. Epub 2014 Aug 27.
BACKGROUND
Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites.
METHODS
Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC).
RESULTS
Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P < .05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P = .014) and rs149979685 (P = .037). These associations were replicated in the ADGC sample (rs144662445: P = .0022, odds ratio [OR] = 2.75; rs149979685: P = .0022, OR = 3.61).
CONCLUSIONS
Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.
背景
与非西班牙裔白人相比，非裔美国人（AA）中阿尔茨海默病（AD）的遗传基础鲜为人知。
方法
对7例AA型AD病例进行了全外显子组测序（WES）。在一个由422例病例和394例对照组成的AA发现队列中，评估了WES中潜在的与AD相关变异的疾病关联性。在来自阿尔茨海默病遗传学联盟（ADGC）的1037例病例和1869例对照的AA样本中寻求复制验证。
结果
WES中的44个单核苷酸多态性（SNP）通过了筛选标准并成功进行了基因分型。在紧密连锁不平衡的两个非洲裔特异性AKAP9 SNP中观察到与AD存在名义上显著（P < 0.05）的关联：rs144662445（P = 0.014）和rs149979685（P = 0.037）。这些关联在ADGC样本中得到了复制（rs144662445：P = 0.0022，比值比[OR] = 2.75；rs149979685：P = 0.0022，OR = 3.61）。
结论
由于AKAP9以前未与AD风险相关联，本研究表明了一种潜在的新疾病机制。
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