title: Non-parametric Survival Analysis of EPG5 Gene with Age at Onset of Alzheimer's Disease.
abstract: Non-parametric methods such as Wilcoxon test have the advantages of no assumptions for the underlying survival distributions. Alzheimer's disease (AD) is a chronic neurodegenerative disease while the ectopic P-granules autophagy protein 5 homolog (EPG5 gene) is highly expressed in human brain and may implicate in the pathogenesis of neurodegenerative disorders. The present study explored the associations of 26 single-nucleotide polymorphisms (SNPs) in the EPG5 gene with the age at onset (AAO) of AD using a family-based association test (FBAT)-Wilcoxon statistic in a family-based study. Then a replication study using a case-control sample was conducted to perform Wilcoxon test in Kaplan-Meier survival analysis of AAO. The results from FBAT-generalized estimating equations (FBAT-GEE) statistics and FBAT-Wilcoxon test showed that seven SNPs (top SNP rs495078 with p = 1.29 × 10-3) were significantly associated with the risk of AD, and eight SNPs (top SNP rs11082498 with p = 3.55 × 10-4) were associated with the AAO of AD in the family-based study (p < 0.05). In the replicated data, three SNPs were associated with AAO by using the Wilcoxon test, where the mean AAO was approximately 2.2 years earlier in individuals who had at least one minor allele of the top AAO-associated SNP rs9963463 (p = 0.0018) compared with those who were homozygous for the major allele. These findings from non-parametric survival analyses provide evidence for several genetic variants in EPG5 influencing the AAO of AD and will serve as a resource for replication in other populations.
authors: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN, 37614-1700, USA. wangk@etsu.edu.
authors: Ke-Sheng
authors: KS
authors: Wang
authors: Department of Systems Leadership and Effectiveness Science, School of Nursing, University of Michigan, Ann Arbor, MI, 48109-5482, USA.
authors: Xuefeng
authors: X
authors: Liu
authors: Division of Biostatistics and Bioinformatics, Department of Environmental Health, University of Cincinnati, Cincinnati, OH, 45267, USA.
authors: Changchun
authors: C
authors: Xie
authors: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN, 37614-1700, USA.
authors: Ying
authors: Y
authors: Liu
authors: Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, 79912, USA.
authors: Chun
authors: C
authors: Xu
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000071183:Autophagy-Related Proteins; D016022:Case-Control Studies; D005260:Female; D006720:Homozygote; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D016019:Survival Analysis; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; C000592185:EPG5 protein, human; D051907:Lysosomal Membrane Proteins; D011506:Proteins; D033921:Vesicular Transport Proteins
keywords: Age at onset; Alzheimer disease; EPG5; Non-parametric methods; Survival analysis; Wilcoxon test