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No Association between SNP rs498055 on Chromosome 10 and Late-Onset Alzheimer Disease in Multiple Datasets
Authors:Xueying Liang  Nathalie Schnetz-Boutaud  Jackie Bartlett  Melissa J Allen  Harry Gwirtsman  Don E Schmechel  Regina M Carney  John R Gilbert  Margaret A Pericak-Vance  Jonathan L Haines
Institution:Center for Human Genetics Research and Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA;
Department of Psychiatry, VA Hospital Medical Center, TN 37232, USA;
Department of Neurology, Duke University, Durham, NC 27710, USA;
Center for Human Genetics, Duke University, Durham, NC 27710, USA;
Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA
Abstract:SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control. All the cases were late-onset AD Caucasian patients with minimum age at onset ≥ 60 years. None of the three family samples or the combined family-based dataset showed association in either allelic or genotypic family-based association tests at p < 0.05. Both original and OSA two-point LOD scores were calculated. However, there was no evidence indicating linkage no matter what covariates were applied (the highest LOD score was 0.82). The case-control dataset did not demonstrate any association between this SNP and AD (all p-values > 0.52). Our results do not confirm the previous association, but are consistent with a more recent negative association result that used family-based association tests to examine the effect of this SNP in two family datasets. Thus we conclude that rs498055 is not associated with an increased risk of LOAD.
Keywords:alzheimer disease  association  chromosome 10  rs498055  SNP
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