Genome screen of late-onset Alzheimer's extended pedigrees identifies TRPC4AP by haplotype analysis

S. E. Poduslo, R. Huang, J. Huang, Suzanne H Smith

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)50-55
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number1
DOIs
StatePublished - Jan 5 2009

Keywords

  • Complex disease
  • Extended pedigrees
  • Genome-wide association study

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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