Association studies of 23 positional/functional candidate genes on chromosome 10 in late‐onset Alzheimer's disease
Copyright policy )Association studies of 23 positional/functional candidate genes on chromosome 10 in late‐onset Alzheimer's disease
AbstractLate‐onset Alzheimer's disease (LOAD) is a common neurodegenerative disorder, with a complex etiology. APOE is the only confirmed susceptibility gene for LOAD. Others remain yet to be found. Evidence from linkage studies suggests that a gene (or genes) conferring susceptibility for LOAD resides on chromosome 10. We studied 23 positional/functional candidate genes from our linkage region on chromosome 10 (APBB1IP, ALOX5, AD037, SLC18A3, DKK1, ZWINT, ANK3, UBE2D1, CDC2, SIRT1, JDP1, NET7, SUPV3L1, NEN3, SAR1, SGPL1, SEC24C, CAMK2G, PP3CB, SNCG, CH25H, PLCE1, ANXV111) in the MRC genetic resource for LOAD. These candidates were screened for sequence polymorphisms in a sample of 14 LOAD subjects and detected polymorphisms tested for association with LOAD in a three‐stage design involving two stages of genotyping pooled DNA samples followed by a third stage in which markers showing evidence for association in the first stages were subjected to individual genotyping. One hundred and twenty polymorphisms were identified and tested in stage 1 (4 case + 4 control pools totaling 366 case and 366 control individuals). Single nucleotide polymorphisms (SNPs) showing evidence of association with LOAD were then studied in stage 2 (8 case + 4 control pools totaling 1,001 case and 1,001 control individuals). Five SNPs, in four genes, showed evidence for association (P < 0.1) at stage 2 and were individually genotyped in the complete dataset, comprising 1,160 LOAD cases and 1,389 normal controls. Two SNPs in SGPL1 demonstrated marginal evidence of association, with uncorrected P values of 0.042 and 0.056, suggesting that variation in SGPL1 may confer susceptibility to LOAD. © 2007 Wiley‐Liss, Inc.
- University of Cambridge United Kingdom
- Cardiff University United Kingdom
- Kings College London, University of London United Kingdom
- Trinity College Dublin Ireland
- St. James's Hospital Ireland
Aged, 80 and over, Male, Genotype, Chromosomes, Human, Pair 10, association, 610, candidate gene, SNP, Chromosome Mapping, DNA, Polymorphism, Single Nucleotide, chromosome 10, Gene Frequency, Alzheimer Disease, Case-Control Studies, Humans, Female, late-onset Alzheimer's disease, Age of Onset, Alleles, Aged
Aged, 80 and over, Male, Genotype, Chromosomes, Human, Pair 10, association, 610, candidate gene, SNP, Chromosome Mapping, DNA, Polymorphism, Single Nucleotide, chromosome 10, Gene Frequency, Alzheimer Disease, Case-Control Studies, Humans, Female, late-onset Alzheimer's disease, Age of Onset, Alleles, Aged
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