A genomewide scan confirmed the apolipoprotein E gene at chromosome 19q13.32 as the strongest locus associated with late-onset Alzheimer disease risk, alongside several other significant loci.
Case-Control (n=2,138)
Are specific genetic loci associated with the risk of late-onset Alzheimer disease?
Several genetic loci, including the apolipoprotein E gene and newly identified variants, are associated with the risk of late-onset Alzheimer disease.
OBJECTIVE: To identify putative genetic loci related to the risk of late-onset Alzheimer disease (LOAD). DESIGN: Linkage analysis and family-based and case-control association analyses from a genomewide scan using approximately 6000 single-nucleotide polymorphic markers at an average intermarker distance of 0.65 cM. SETTING: The National Institute on Aging Genetics Initiative for Late-Onset Alzheimer's Disease (NIA-LOAD) was created to expand the resources for studies to identify additional genes contributing to the risk for LOAD. PARTICIPANTS: We investigated 1902 individuals from 328 families with LOAD and 236 unrelated control subjects. MAIN OUTCOME MEASURES: Clinical diagnosis of LOAD. RESULTS: The strongest overall finding was at chromosome 19q13.32, confirming the effect of the apolipoprotein E gene on LOAD risk in the family-based and case-control analyses. However, single-nucleotide polymorphisms at the following loci were also statistically significant in 1 or more of the analyses performed: 7p22.2, 7p21.3, and 16q21 in the linkage analyses; 17q21.31 and 22q11.21 in the family-based association analysis; and 7q31.1 and 22q12.3 in the case-control analysis. Positive associations at 7q31.1 and 20q13.33 were also significant in the meta-analysis results in a publicly available database. CONCLUSIONS: Several additional loci may harbor genetic variants associated with LOAD. This data set provides a wealth of phenotypic and genotypic information for use as a resource in discovery and confirmatory research.
Joseph H. Lee (Mon,) conducted a case-control in Late-onset Alzheimer disease (LOAD) (n=2,138). Genetic variants (genomewide scan) vs. Unrelated control subjects was evaluated on Clinical diagnosis of LOAD. A genomewide scan confirmed the apolipoprotein E gene at chromosome 19q13.32 as the strongest locus associated with late-onset Alzheimer disease risk, alongside several other significant loci.