Follow-Up Study of Susceptibility Loci for Alzheimer's Disease and Onset Age Identified by Genome-Wide Association
Bettens, Karolien × Brouwers, Nathalie Van Miegroet, Helen Gil, Ana Engelborghs, Sebastiaan De Deyn, Peter P Vandenberghe, Rik Van Broeckhoven, Christine Sleegers, Kristel #
Journal of Alzheimer's Disease vol:19 issue:4 pages:1169-1175
Replication of genetic association findings in independent studies represents an important validation tool in the search for susceptibility genes for complex diseases such as Alzheimer's disease (AD). In a well-characterized memory-clinic based study comprising 1078 unrelated AD patients and 652 control individuals, we set out to replicate previously reported genome-wide association of four novel risk SNPs with AD and onset age, with first stage p-values ranging from 0.001 to 0.000004. We obtained evidence for association between rs179943, an intronic SNP in ATXN1 at 6p22.3, and affection status (OR = 0.63 (95% CI = 0.44-0.90; nominal p = 0.01)). Overall, our data provided independent support for association of at least one chromosomal locus with AD and warranted a more in-depth investigation of these regions for possible underlying functional variants.