Identification of Novel Loci for Alzheimer Disease and Replication of CLU, PICALM, and BIN1 in Caribbean Hispanic Individuals

被引:146
作者
Lee, Joseph H. [1 ,5 ,6 ]
Cheng, Rong [1 ]
Barral, Sandra [1 ,2 ]
Reitz, Christiane [1 ,2 ]
Medrano, Martin [7 ]
Lantigua, Rafael [1 ,4 ]
Jimenez-Velazquez, Ivonne Z. [8 ]
Rogaeva, Elzaterina [9 ,10 ]
George-Hyslop, Peter H. St. [9 ,10 ,11 ,12 ]
Mayeux, Richard [1 ,2 ,3 ,5 ,6 ]
机构
[1] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA
[2] Columbia Univ, Dept Neurol, New York, NY USA
[3] Columbia Univ, Dept Psychiat, New York, NY USA
[4] Columbia Univ, Dept Med, New York, NY USA
[5] Columbia Univ, Coll Phys & Surg, New York, NY USA
[6] Columbia Univ, Sch Publ Hlth, Dept Epidemiol, New York, NY USA
[7] Univ Tecnolog Santiago, Santiago, Dominican Rep
[8] Univ Puerto Rico, Sch Med, Dept Internal Med, San Juan, PR 00936 USA
[9] Univ Toronto, Dept Med, Ctr Res Neurodegenerat Dis, Lab Med & Pathobiol & Med Biophys, Toronto, ON, Canada
[10] Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada
[11] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England
[12] Univ Cambridge, Dept Clin Neurosci, Cambridge, England
基金
英国惠康基金; 加拿大健康研究院; 美国国家卫生研究院;
关键词
GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; POPULATION; RISK; APOE; VARIANTS; POLYMORPHISMS; DIAGNOSIS; REVEALS; PROTEIN;
D O I
10.1001/archneurol.2010.292
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 X 10(-7)), but 22 additional single-nucleotide polymorphisms (SNPs) had a P value less than 9 X 10(-6) under 3 different analyses: unadjusted and stratified by the presence or absence of the APOE 64 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.
引用
收藏
页码:320 / 328
页数:9
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