- Home
- About
- Collaborative Data Access (SAGs)
- Publications
- For Members
Title | Genome scan in familial late-onset Alzheimer's disease: a locus on chromosome 6 contributes to age-at-onset. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Zhao W, Marchani EE, Cheung CYK, Steinbart EJ, Schellenberg GD, Bird TD, Wijsman EM |
Journal | Am J Med Genet B Neuropsychiatr Genet |
Volume | 162B |
Issue | 2 |
Pagination | 201-12 |
Date Published | 2013 Mar |
ISSN | 1552-485X |
Keywords | Age of Onset, Aged, Alzheimer Disease, Apolipoproteins E, Chromosome Segregation, Chromosomes, Human, Pair 6, Female, Genetic Linkage, Genetic Loci, Genome, Human, Humans, Male, Models, Genetic, Quantitative Trait Loci, Quantitative Trait, Heritable |
Abstract | Alzheimer's disease (AD) is a common, genetically complex, fatal neurodegenerative disorder of late life. Although several genes are known to play a role in early-onset AD, identification of the genetic basis of late onset AD (LOAD) has been challenging, with only the APOE gene known to have a high contribution to both AD risk and age-at-onset. Here, we present the first genome-scan analysis of the complete, well-characterized University of Washington LOAD sample of 119 pedigrees, using age-at-onset as the trait of interest. The analysis approach used allows for a multilocus trait model while at the same time accommodating age censoring, effects of APOE as a known genetic covariate, and full pedigree and marker information. The results provide strong evidence for linkage of loci contributing to age-at-onset to genomic regions on chromosome 6q16.3, and to 19q13.42 in the region of the APOE locus. There was evidence for interaction between APOE and the locus on chromosome 6q and suggestive evidence for linkage to chromosomes 11p13, 15q12-14, and 19p13.12. These results provide the first independent confirmation of an AD age-at-onset locus on chromosome 6 and suggest that further efforts towards identifying the underlying causal locus or loci are warranted. |
DOI | 10.1002/ajmg.b.32133 |
Alternate Journal | Am. J. Med. Genet. B Neuropsychiatr. Genet. |
PubMed ID | 23355194 |
PubMed Central ID | PMC3654841 |
Grant List | K99 AG040184 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States T32 AG000258 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States |