P3–020: ADGC+: An expanded Alzheimer's Disease Genetics Consortium (ADGC) genome‐wide association study
Year: 2013
Type: article
Abstract: Genome-wide association studies (GWAS) are useful for identifying common variants that increase genetic susceptibility for Alzheimer's disease. Recent GWAS have identified and confirmed nine novel AD susceptibility loci besides APOE in recent years, including ABCA7, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, MS4A4, and PICALM. Between 2008 and 2011, for each round of gene discovery, increases in sample size not only confirmed the validity of earlier findings, but also identified novel genes. To identify additional AD loci, the ADGC is currently performing a new GWAS on a combined dataset that has a substantial increase in sample size over our previously published 2011 GWAS. Association analysis is ongoing using logistic regression for case-control datasets and generalized estimating equations for datasets that include family members. For both family and case-control datasets genotype will be modeled using an additive model on the dosage of the minor allele. Age at onset/exam, gender, and variables for population substructure will be included as covariates. Data will then be analyzed across the datasets using a meta-analysis approach. Other analyses such as gene-gene interaction analysis and pathway analyses will also be performed. The initial ADGC GWAS consisted of fifteen datasets genotyped using genome-wide genotyping platforms (Illumina or Affymetrix) on a total of 11,840 cases and 10,931 controls. For the combined ADGC GWAS we have added cases and controls not previously included from these datasets, as well as samples from several new datasets (2,550 cases/4351 controls) for a combined total of 14,390 cases and 15,282 controls. Power studies showed that increasing the sample size results in as much as a 90% increase in power to detect small odds ratios. For example, in the original GWAS, we had only 40% power to detect an odds ratio of 1.1 at a significance level or 10–8 (MAF=0.5), but in the combined sample, power increases to 75%. All cases meet standard clinical LOAD definitions (or were confirmed through autopsy); controls are age-matched to cases and are cognitively intact at exam. Genotype imputation is to the December 2012 release of the 1,000 Genomes Project data. Analysis is ongoing and will be presented.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2071358473