Dataset Information

Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

ABSTRACT: In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in unusually large data sets, and previously implicated CST3 and ACE SNPs. In the cases of CLU, PICALM and CR1, as well as in APOE, the odds ratios we find are slightly larger than those previously reported in clinical samples, consistent with what we believe to be more accurate classification of disease in the clinically characterized and neuropathologically confirmed AD cases and controls.

SUBMITTER: Corneveaux JJ

PROVIDER: S-EPMC2908469 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

Corneveaux Jason J JJ Myers Amanda J AJ Allen April N AN Pruzin Jeremy J JJ Ramirez Manuel M Engel Anzhelika A Nalls Michael A MA Chen Kewei K Lee Wendy W Chewning Kendria K Villa Stephen E SE Meechoovet Hunsar B HB Gerber Jill D JD Frost Danielle D Benson Hollie L HL O'Reilly Sean S Chibnik Lori B LB Shulman Joshua M JM Singleton Andrew B AB Craig David W DW Van Keuren-Jensen Kendall R KR Dunckley Travis T Bennett David A DA De Jager Philip L PL Heward Christopher C Hardy John J Reiman Eric M EM Huentelman Matthew J MJ

Human molecular genetics 20100609 16

In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in ...[more]

PMID: 20534741

Similar Datasets

Project description:BackgroundGenetic variants at the CLU, CR1, and PICALM loci associate with risk for late-onset Alzheimer's disease (LOAD) in genomewide association studies. In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in black and white subjects.MethodsWe pursued an association study between single nucleotide polymorphism genotypes at the CLU, CR1, and PICALM loci and memory endophenotypes. We assessed black subjects (AA series: 44 with LOAD and 224 control subjects) recruited at Mayo Clinic Florida and whites recruited at Mayo Clinic Minnesota (RS series: 372 with LOAD and 1690 control subjects) and Florida (JS series: 60 with LOAD and 529 control subjects). Single nucleotide polymorphisms at the LOAD risk loci CLU (rs11136000), CR1 (rs6656401, rs3818361), and PICALM (rs3851179) were genotyped and tested for association with Logical Memory immediate recall, Logical Memory delayed recall, Logical Memory percent retention, Visual Reproduction immediate recall, Visual Reproduction delayed recall, and Visual Reproduction percent retention scores from the Wechsler Memory Scale-Revised using multivariable linear regression analysis, adjusting for age at exam, sex, education, and apolipoprotein E ε4 dosage.ResultsWe identified nominally significant or suggestive associations between the LOAD-risky CR1 variants and worse Logical Memory immediate recall scores in blacks (P = .068-.046, β = -2.7 to -1.2). The LOAD-protective CLU variant is associated with better logical memory endophenotypes in white subjects (P = .099-.027, β = 0.31-0.93). The CR1 associations persisted when the control subjects from the AA series were assessed separately. The CLU associations appeared to be driven by one of the white series (RS) and were also observed when the control subset from RS was analyzed.ConclusionThese results suggest for the first time that LOAD risk variants at CR1 may influence memory endophenotypes in blacks. In addition, the CLU LOAD-protective variant may confer enhanced memory in whites. Although these results would not remain significant after stringent corrections for multiple testing, they need to be considered in the context of the LOAD associations with which they have biological consistency. They also provide estimates for effect sizes on memory endophenotypes that could guide future studies. The detection of memory effects for these variants in clinically normal subjects, implies that these LOAD risk loci might modify memory prior to clinical diagnosis of AD.

Dataset Information

Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

Publications

Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets