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

作者：Li Yonghong^*; Rowland Charles; Catanese Joseph; Morris John C; Lovestone Simon; O'Donovan Michael C; Goate Alison; Owen Michael; Williams Julie; Grupe Andrew

来源：Neurobiology of Disease, 2008, 29(2): 293-296.

DOI：10.1016/j.nbd.2007.09.001

• Alzheimer's disease
• single nucleotide polymorphism
• haplotype
• association study
• SORL1

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.

• 出版日期2008-2