Please cite this article as follows: Poduslo SE, Huang R, Huang J, Smith S. 2008. Genome Screen of Late-Onset Alzheimer's Extended Pedigrees Identifies TRPC4AP by Haplotype Analysis. Am J Med Genet Part B 150B:50–55.
Genome screen of late-onset Alzheimer's extended pedigrees identifies TRPC4AP by haplotype analysis†
Article first published online: 30 APR 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 1, pages 50–55, 5 January 2009
How to Cite
Poduslo, S.E., Huang, R., Huang, J. and Smith, S. (2009), Genome screen of late-onset Alzheimer's extended pedigrees identifies TRPC4AP by haplotype analysis. Am. J. Med. Genet., 150B: 50–55. doi: 10.1002/ajmg.b.30767
- Issue published online: 21 JAN 2009
- Article first published online: 30 APR 2008
- Manuscript Accepted: 25 MAR 2008
- Manuscript Received: 18 JAN 2008
- VA Merit award, MCG funds, National Institute of Aging for the National Cell Repository. Grant Number: U2AG21886
- complex disease;
- genome-wide association study;
- extended pedigrees
Alzheimer's disease is a complex progressive neurodegenerative disorder with profound cognitive decline. Multiple susceptibility genetic variants have been identified with equivocal replication. While rare, collections of extended pedigrees with multiple affected family members are invaluable for genome-wide screens. We have used two extended pedigrees, having 14–15 siblings with four to five affected late-onset Alzheimer's disease patients in each, to identify the gene, transient receptor potential cation channel, subfamily C, member 4 associated protein (TRPC4AP), on chromosome 20q11.22, as relevant for the disease. Multiple significant SNPs in this gene were found with the initial genome scan (after Bonferroni correction). Additional SNPs were assessed in the families and in the controls which were also significant by haplotype analysis. Moreover, 36% of the patients' haplotypes in our collection of late-onset patients had the same haplotype. These results suggest that TRPC4AP is involved with the disease in these late-onset Alzheimer's families. The results also confirm the use of the genome-wide association study for identifying new genetic variants of complex diseases. © 2008 Wiley-Liss, Inc.