The MAPT gene that encodes Tau is located on chromosome 17q21, in a region, which has evolved to form two major haplotypes, H1 and H2. There is strong evidence that the H1 haplotype, and a sub-haplotype (H1C), are overrepresented and associated with increased risk for the sporadic tauopathies, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Both PSP and CBD cases display Tau pathology similar to Late-Onset Alzheimer's Disease (LOAD). However, numerous association studies investigating the genetic involvement of MAPT in LOAD have generated conflicting results. Here we have used a large LOAD case-control sample to genotype SNPs that have been shown to define H1/H2 status and intra-H1 variability. Singlemarker association analyses found no evidence that any of the SNPs are associated with risk of LOAD. When gender and APOE4 status were taken into account we observed suggestive association for SNP rs242557 (P=0.02). Stratification of the sample revealed association with rs242557 only in APOE4 positive individuals (P=0.01 recessive model), however this result would not survive multiple correction. There was no significant difference in H1/H2 haplotype distribution between cases and controls. We also tested the association of specific subhaplotypes on the H1 background and likewise results were negative. No effect was observed on disease age of onset for any of the markers studied. In summary, we find no evidence for allelic or haplotypic association, with SNPs in the MAPT gene and LOAD. SNP rs242557 is nominally significant in the APOE4 positive individuals. None of the SNPs studied modified AAO for LOAD. © 2009 Wiley-Liss, Inc.
Abraham, R., Sims, R., Carroll, L., Hollingworth, P., O’Donovan, M. C., Williams, J., & Owen, M. J. (2009). An association study of common variation at the MAPT locus with late-onset Alzheimer’s disease. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 150(8), 1152–1155. https://doi.org/10.1002/ajmg.b.30951