Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.

TitleAnalyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.
Publication TypeJournal Article
Year of Publication2008
AuthorsLee, JH, Cheng, R, Graff-Radford, N, Foroud, T, Mayeux, R
Corporate AuthorsNational Institute on Aging Late-Onset Alzheimer's Disease Family Study Group
JournalArch Neurol
Volume65
Issue11
Pagination1518-26
Date Published2008 Nov
ISSN1538-3687
KeywordsAlzheimer Disease, Apolipoproteins E, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 7, Genetic Linkage, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Humans, National Institute on Aging (U.S.), Polymorphism, Single Nucleotide, United States
Abstract

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.

DOI10.1001/archneur.65.11.1518
Alternate JournalArch. Neurol.
PubMed ID19001172
PubMed Central IDPMC2694670
Grant ListP01 AG007232-20 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
N01HG65403 / HG / NHGRI NIH HHS / United States
P50AG08702 / AG / NIA NIH HHS / United States
P30 AG010133 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01 AG027342 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
P50 AG008702-199006 / AG / NIA NIH HHS / United States
U24 AG026395-04 / AG / NIA NIH HHS / United States
P01AG05138 / AG / NIA NIH HHS / United States
P01 AG007232 / AG / NIA NIH HHS / United States
P30AG010124 / AG / NIA NIH HHS / United States
U24AG021886 / AG / NIA NIH HHS / United States
R01 AG027224-02 / AG / NIA NIH HHS / United States
R37 AG015473-11 / AG / NIA NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
P30AG010133 / AG / NIA NIH HHS / United States
R01 AG041797 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
R01 AG027224 / AG / NIA NIH HHS / United States
U24AG026395 / AG / NIA NIH HHS / United States
P30AG028377 / AG / NIA NIH HHS / United States