Premium
Genome scan in familial late‐onset Alzheimer's disease: A locus on chromosome 6 contributes to age‐at‐onset
Author(s) -
Zhao Wei,
Marchani Elizabeth E.,
Cheung Charles Y.K.,
Steinbart Ellen J.,
Schellenberg Gerard D.,
Bird Thomas D.,
Wijsman Ellen M.
Publication year - 2013
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32133
Subject(s) - locus (genetics) , genetics , genome scan , age of onset , biology , genetic linkage , apolipoprotein e , quantitative trait locus , chromosome 19 , disease , pedigree chart , chromosome , allele , gene , medicine , microsatellite
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. © 2013 Wiley Periodicals, Inc.