title: Genome-wide haplotype association study identify TNFRSF1A, CASP7, LRP1B, CDH1 and TG genes associated with Alzheimer's disease in Caribbean Hispanic individuals.
abstract: Alzheimer's disease (AD) is an acquired disorder of cognitive and behavioral impairment. It is considered to be caused by variety of factors, such as age, environment and genetic factors. In order to identify the genetic affect factors of AD, we carried out a bioinformatic approach which combined genome-wide haplotype-based association study with gene prioritization. The raw SNP genotypes data was downloaded from GEO database (GSE33528). It contains 615 AD patients and 560 controls of Caribbean Hispanic individuals. Firstly, we identified the linkage disequilibrium (LD) haplotype blocks and performed genome-wide haplotype association study to screen significant haplotypes that were associated with AD. Then we mapped these significant haplotypes to genes and obtained candidate genes set for AD. At last, we prioritized AD candidate genes based on their similarity with 36 known AD genes, so as to identify AD related genes. The results showed that 141 haplotypes on 134 LD blocks were significantly associated with AD (P<1E-4), and these significant haplotypes were mapped to 132 AD candidate genes. After prioritizing these candidate genes, we found seven AD related genes: APOE, APOC1, TNFRSF1A, LRP1B, CDH1, TG and CASP7. Among these genes, APOE and APOC1 are known AD risk genes. For the other five genes TNFRSF1A, CDH1, CASP7, LRP1B and TG, this is the first genetic association study which showed the significant association between these five genes and AD susceptibility in Caribbean Hispanic individuals. We believe that our findings can provide a new perspective to understand the genetic affect factors of AD.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Shang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Lv
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Duan
authors.affiliation: Genetic Data Analysis Group, The Genome Science Consortium, Harbin, China.
authors.forename: Situo
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ruijie
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D017691:Caribbean Region; D053179:Caspase 7 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008840:Microfilament Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C434476:LRP1B protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011973:Receptors, LDL; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; C051615:transgelin; C505520:CASP7 protein, human; D053179:Caspase 7
keywords: Alzheimer’s disease; Pathology Section; haplotype association analysis