Archives of neurology · 2010
Identification of novel loci for Alzheimer disease and replication of CLU, PICALM, and BIN1 in Caribbean Hispanic individuals.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Lee Joseph H, Cheng Rong, Barral Sandra, Reitz Christiane, Medrano Martin, Lantigua Rafael, Jiménez-Velazquez Ivonne Z, Rogaeva Ekaterina, St George-Hyslop Peter H, Mayeux Richard
Аннотация
OBJECTIVES: To identify novel loci for late-onset Alzheimer disease (LOAD) in Caribbean Hispanic individuals and to replicate the findings in a publicly available data set from the National Institute on Aging Late-Onset Alzheimer's Disease Family Study.
DESIGN: Nested case-control genome-wide association study.
SETTING: The Washington Heights-Inwood Columbia Aging Project and the Estudio Familiar de Influencia Genetica de Alzheimer study.
PARTICIPANTS: Five hundred forty-nine affected and 544 unaffected individuals of Caribbean Hispanic ancestry.
INTERVENTION: The Illumina HumanHap 650Y chip for genotyping.
MAIN OUTCOME MEASURE: Clinical diagnosis or pathologically confirmed diagnosis of LOAD.
RESULTS: The strongest support for allelic association was for rs9945493 on 18q23 (P=1.7×10(-7)), but 22 additional single-nucleotide polymorphisms (SNPs) had a P value less than 9×10(-6) under 3 different analyses: unadjusted and stratified by the presence or absence of the APOE ε4 allele. Of these SNPs, 5 SNPs (rs4669573 and rs10197851 on 2p25.1; rs11711889 on 3q25.2; rs1117750 on 7p21.1; and rs7908652 on 10q23.1) were associated with LOAD in an independent cohort from the National Institute on Aging Late-Onset Alzheimer's Disease Family Study. We also replicated genetic associations for CLU, PICALM, and BIN1.
CONCLUSIONS: Our genome-wide search of Caribbean Hispanic individuals identified several novel genetic variants associated with LOAD and replicated these associations in a white cohort. We also replicated associations in CLU, PICALM, and BIN1 in the Caribbean Hispanic cohort.
DESIGN: Nested case-control genome-wide association study.
SETTING: The Washington Heights-Inwood Columbia Aging Project and the Estudio Familiar de Influencia Genetica de Alzheimer study.
PARTICIPANTS: Five hundred forty-nine affected and 544 unaffected individuals of Caribbean Hispanic ancestry.
INTERVENTION: The Illumina HumanHap 650Y chip for genotyping.
MAIN OUTCOME MEASURE: Clinical diagnosis or pathologically confirmed diagnosis of LOAD.
RESULTS: The strongest support for allelic association was for rs9945493 on 18q23 (P=1.7×10(-7)), but 22 additional single-nucleotide polymorphisms (SNPs) had a P value less than 9×10(-6) under 3 different analyses: unadjusted and stratified by the presence or absence of the APOE ε4 allele. Of these SNPs, 5 SNPs (rs4669573 and rs10197851 on 2p25.1; rs11711889 on 3q25.2; rs1117750 on 7p21.1; and rs7908652 on 10q23.1) were associated with LOAD in an independent cohort from the National Institute on Aging Late-Onset Alzheimer's Disease Family Study. We also replicated genetic associations for CLU, PICALM, and BIN1.
CONCLUSIONS: Our genome-wide search of Caribbean Hispanic individuals identified several novel genetic variants associated with LOAD and replicated these associations in a white cohort. We also replicated associations in CLU, PICALM, and BIN1 in the Caribbean Hispanic cohort.
Предметные рубрики MeSH
Adaptor Proteins, Signal TransducingAge of OnsetAgedAged, 80 and overAllelesAlzheimer DiseaseApolipoproteins EBlack PeopleCaribbean RegionClusterinCohort StudiesData Interpretation, StatisticalFemaleGene FrequencyGenome-Wide Association StudyGenotypeHispanic or LatinoHumansMaleMonomeric Clathrin Assembly ProteinsNuclear ProteinsPolymorphism, Single NucleotideTumor Suppressor ProteinsWhite People