Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.
OBJECTIVE
To identify putative genetic loci related to the risk of late-onset Alzheimer disease (LOAD).


METHODS
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.


METHODS
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.


METHODS
We investigated 1902 individuals from 328 families with LOAD and 236 unrelated control subjects.


METHODS
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.
Lee
Joseph H
JH
Gertrude H. Sergievsky Center, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Cheng
Rong
R
Graff-Radford
Neill
N
Foroud
Tatiana
T
Mayeux
Richard
R
D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002888:Chromosomes, Human, Pair 19; D002892:Chromosomes, Human, Pair 22; D002897:Chromosomes, Human, Pair 7; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D054561:National Institute on Aging (U.S.); D020641:Polymorphism, Single Nucleotide; D014481:United States
D001057:Apolipoproteins E