SORL1 variants and risk of late-onset Alzheimer's disease

NEUROBIOLOGY OF DISEASE

卷:29

Article

Li, Yonghong¹  Rowland, Charles¹  Catanese, Joseph¹  Morris, John C.^2,3,4  Lovestone, Simon⁵  O'Donovan, Michael C.^6,7  Goate, Alison^2,3  Owen, Michael⁶  Williams, Julie^6,7  Grupe, Andrew¹ 

[1] Celera, Alameda, CA USA

[2] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[5] Kings Coll London, Inst Psychiat, MRC Ctr Neurodegenerat Res, London, England

[6] Cardiff Univ, Sch Med, Dept Psychol Med & Biostat, Cardiff, S Glam, Wales

[7] Cardiff Univ, Sch Med, Bioinformat Unit, Cardiff, S Glam, Wales

关键词: Alzheimer's disease;    single nucleotide polymorphism;    haplotype;    association study;    SORL1;   

DOI  :  10.1016/j.nbd.2007.09.001

来源: Elsevier

【 摘 要 】

A recent study reported significant association of late-onset Alzheimer's disease (LOAD) with multiple single nucleotide polymorphisms (SNPs) and haplotypes in SORL1, a neuronal sortilin-related receptor protein known to be involved in the trafficking and processing of amyloid precursor protein. Here we attempted to validate this finding in three large, well characterized case-control series. Approximately 2000 samples from the three series were individually genotyped for 12 SNPs, including the 10 reported significant SNPs and 2 that constitute the reported significant haplotypes. A total of 25 allelic and haplotypic association tests were performed. One SNP rs2070045 was marginally replicated in the three sample sets combined (nominal P=0.035); however, this result does not remain significant when accounting for multiple comparisons. Further validation in other sample sets will be required to assess the true effects of SORL1 variants in LOAD. (C) 2007 Elsevier Inc. All rights reserved.

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