Analyses of the national institute on aging late-onset Alzheimer's disease family study: Implication of additional loci

Joseph H. Lee, Rong Cheng, Neill Graff-Radford, Tatiana Foroud, Richard Mayeux

Research output: Contribution to journalArticle

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Abstract

Objective: To identify putative genetic loci related to the risk of late-onset Alzheimer disease (LOAD). Design: Linkage analysis and family-based and casecontrol 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:Weinvestigated 1902 individuals from 328 families with LOAD and 236 unrelated control subjects. Main Outcome Measures: Clinical diagnosis of LOAD. Results: Thestrongest overall finding was atchromosome 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;17q21.31and22q11. 21inthefamily-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.

Original languageEnglish
Pages (from-to)1518-1526
Number of pages9
JournalArchives of Neurology
Volume65
Issue number11
DOIs
StatePublished - Nov 2008

Fingerprint

National Institute on Aging (U.S.)
Alzheimer Disease
Genetic Loci
Onset
Alzheimer's Disease
Locus
Apolipoproteins E
Genes
Single Nucleotide Polymorphism
Meta-Analysis
Nucleotides
Outcome Assessment (Health Care)
Databases

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Analyses of the national institute on aging late-onset Alzheimer's disease family study : Implication of additional loci. / Lee, Joseph H.; Cheng, Rong; Graff-Radford, Neill; Foroud, Tatiana; Mayeux, Richard.

In: Archives of Neurology, Vol. 65, No. 11, 11.2008, p. 1518-1526.

Research output: Contribution to journalArticle

Lee, Joseph H. ; Cheng, Rong ; Graff-Radford, Neill ; Foroud, Tatiana ; Mayeux, Richard. / Analyses of the national institute on aging late-onset Alzheimer's disease family study : Implication of additional loci. In: Archives of Neurology. 2008 ; Vol. 65, No. 11. pp. 1518-1526.
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