Conflicts of interest: nothing to declare.
Article first published online: 25 JAN 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 162, Issue 2, pages 201–212, March 2013
How to Cite
Zhao, W., Marchani, E. E., Cheung, C. Y.K., Steinbart, E. J., Schellenberg, G. D., Bird, T. D. and Wijsman, E. M. (2013), Genome scan in familial late-onset Alzheimer's disease: A locus on chromosome 6 contributes to age-at-onset. Am. J. Med. Genet., 162: 201–212. doi: 10.1002/ajmg.b.32133
How to Cite this Article: Zhao W, Marchani EE, Cheung CYK, Steinbart EJ, Schellenberg GD, Bird TD, Wijsman EM. 2013. Genome Scan in Familial Late-Onset Alzheimer's Disease: A Locus on Chromosome 6 Contributes to Age-at-Onset. Am J Med Genet Part B 162B:201–212.
- Issue published online: 21 FEB 2013
- Article first published online: 25 JAN 2013
- Manuscript Accepted: 26 DEC 2012
- Manuscript Received: 14 JUN 2012
- National Institutes of Health (NIH). Grant Numbers: P50 AG005136, T32 AG000258, K99 AG040184, U24 AG021886
- Veterans Affairs Research Funds
- Metropolitan Life Foundation
- linkage analysis;
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.