title: Genetic Determinants of Survival in Patientswith Alzheimer’s Disease.
abstract: There is a strong genetic basis for late-onset of Alzheimer’s disease (LOAD), and thus far >20 genes/loci have been identified that affect the risk of LOAD. In addition to disease risk, genetic variation at these loci may also affect components of the natural history of AD, such as survival in AD. In this study, we first examined the role of known LOAD genes with survival time in 983 AD patients. We then performed genome-wide single-nucleotide polymorphism (SNP) and gene-based association analyses to identify novel loci that may influence survival of AD. Survival analysis was conducted using Cox proportional hazards regression under an additive genetics model. We found multiple nominally significant associations (p < 0.01) either within or adjacent to known LOAD genes. Genome-wide SNP analysis identified multiple suggestive novel loci and two of them were also significant in gene-based analysis (CCDC85C and NARS2) that survived after controlling for false-discovery rate at 0.05. In summary, we have identified two novel genes for survival in AD that need to be replicated in independent samples. Our findings highlight the importance of focusing on AD-related phenotypes that may help to identify additional genes relevant toAD.
authors: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Xingbin
authors: X
authors: Wang
authors: Oscar
authors: O
authors: Lopez
authors: Robert A
authors: RA
authors: Sweet
authors: James T
authors: JT
authors: Becker
authors: Steven T
authors: ST
authors: DeKosky
authors: Mahmud M
authors: MM
authors: Barmada
authors: Eleanor
authors: E
authors: Feingold
authors: F Yesim
authors: FY
authors: Demirci
authors: M Ilyas
authors: MI
authors: Kamboh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000401:mortality*; D001226:Aspartate-tRNA Ligase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001226:Aspartate-tRNA Ligase; C000601756:NARS2 protein, human
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