Further evidence of a maternal parent-of-origin effect on chromosome 10 in late-onset Alzheimer's disease

Susan Spear Bassett, Dimitrios Avramopoulos, Rodney T. Perry, Howard Wiener, Bracie Watson, Rodney C.P. Go, M. Daniele Fallin

Research output: Contribution to journalArticle

Abstract

The chromosome 10q region has recently received a great deal of attention in late-onset Alzheimer's disease (LOAD), given the growing evidence of linkage to LOAD, or to A-beta levels, reported by several groups. In a recent paper we reported evidence of linkage in this region in our subset of the NIMH AD genetics initiative pedigrees, approaching genome-wide significance (non-parametric LOD score = 3.27), when only families with maternal disease origin were analyzed [Bassett et al. (2002); Am J Med Genet 114:679-686]. We have now extended this work, using an independent subset of NIMH AD pedigrees from the University of Alabama at Birmingham (UAB), and show further evidence of linkage using parent-of-origin information. As in our Hopkins sample, maternal but not paternal pedigrees show significantly increased linkage in the chromosome 10q region compared to the unstratified sample. Combining data from our previous fine-mapping work on this region and five new markers genotyped in all pedigrees results in a non-parametric LOD score of 3.73 in the same region, a value that reaches genome wide significance for linkage, with an empirical P value = 0.003. These results support our earlier findings and narrow the region of interest. In combination with findings from other groups, these results provide further evidence that this chromosome 10 region harbors a gene implicated in LOAD, and our use of parent-of-origin information has been useful in further narrowing the region of interest.

Original languageEnglish (US)
Pages (from-to)537-540
Number of pages4
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume141
Issue number5
DOIs
StatePublished - Jul 5 2006

Keywords

  • Alzheimer's disease
  • Genetic imprinting
  • Human chromosome 10
  • Linkage

ASJC Scopus subject areas

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

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