Archives of neurology · 2008
Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Lee Joseph H, Cheng Rong, Graff-Radford Neill, Foroud Tatiana, Mayeux Richard, National Institute on Aging Late-Onset Alzheimer's Disease Family Study Group
Аннотация
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.
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.
Предметные рубрики MeSH
Alzheimer DiseaseApolipoproteins ECase-Control StudiesChromosome MappingChromosomes, Human, Pair 16Chromosomes, Human, Pair 19Chromosomes, Human, Pair 22Chromosomes, Human, Pair 7Genetic LinkageGenetic Predisposition to DiseaseGenetic VariationGenome, HumanHumansNational Institute on Aging (U.S.)Polymorphism, Single NucleotideUnited States