title: SORL1 variants and risk of late-onset Alzheimer's disease.
abstract: 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.
authors.affiliation: Celera, 1401 Harbor Bay Parkway, Alameda, CA, USA. yonghong.li@celera.com
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.forename: Charles
authors.initials: C
authors.lastname: Rowland
authors.forename: Joseph
authors.initials: J
authors.lastname: Catanese
authors.forename: John
authors.initials: J
authors.lastname: Morris
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Michael
authors.initials: M
authors.lastname: Owen
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Andrew
authors.initials: A
authors.lastname: Grupe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human