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01.06.2004 | Original Article

Evidence of linkage and association on chromosome 20 for late-onset Alzheimer disease

verfasst von: Katrina A. B. Goddard, Jane M. Olson, Haydeh Payami, Monique van der Voet, Helena Kuivaniemi, Gerard Tromp

Erschienen in: Neurogenetics | Ausgabe 2/2004

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Abstract

Recently, we reported evidence of linkage on chromosome 20 for Alzheimer disease (AD) using a novel statistical approach to incorporate covariates (e.g., age, ApoE genotype) into the analysis. These results suggest that very elderly subjects (>85 years), and individuals who carry an ε2 allele at the ApoE locus are more likely to be linked to this candidate region. The region on chromosome 20 includes a strong candidate gene, cystatin C (CST3), which has previously been associated with AD in case-control studies. We investigated these findings further by genotyping additional markers to narrow the candidate region, and to identify evidence of linkage disequilibrium as additional support for a susceptibility locus on chromosome 20. We selected 43 elderly sibships (89 subjects) from the NIMH AD Genetics Initiative based on current age older than 84 years, and identified 129 unrelated control subjects who were older than 84 years from the Oregon Brain Aging Study to conduct linkage and association studies in this region. Fourteen additional markers were evaluated, including 4 markers located within or near CST3. We narrowed the candidate region on chromosome 20 to an 11.8-cM region between markers D20S174 and D20S471, which includes the CST3 candidate gene. In addition, we observed evidence of association for markers located near the CST3 candidate gene, with P values between 0.002 and 0.08 for two-locus haplotypes. These results support the presence of a susceptibility locus for AD in the vicinity of CST3 for very elderly subjects with AD.

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Titel: Evidence of linkage and association on chromosome 20 for late-onset Alzheimer disease
verfasst von: Katrina A. B. Goddard
Jane M. Olson
Haydeh Payami
Monique van der Voet
Helena Kuivaniemi
Gerard Tromp
Publikationsdatum: 01.06.2004
Verlag: Springer-Verlag
Erschienen in: Neurogenetics / Ausgabe 2/2004
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-004-0174-3

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