Copy number polymorphism at chromosome 19 locus associated with late-onset Alzheimer's disease

cerebrospinal fluid (CSF) series. Association analyses were performed using ANCOVA after adjustment for covariates. Power analyses were performed using PROC POWER in SAS. Results: We failed to detect association between CSF Ab42 levels and SNPs in SORL1 despite substantial statistical power to detect association. While we also failed to detect association between variants in GAB2 and CSF tau levels power to detect this association was limited. Finally, our data suggest that the minor allele of rs2986017, in CALHM1, is significantly associated with CSF Ab42 levels (p 1⁄4 0.0095). Conclusions: This association is consistent with previous reports suggesting that this non-synonymous coding substitution results in increased Ab levels in vitro and provides support for an Ab-related mechanism for modulating risk for AD. This finding provides further evidence that the use of CSF endophenotypes for genetic studies of AD can be an effective tool for understanding the biological mechanisms by which variants influence risk for LOAD.