Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis

Ping I. Lin, Eden R. Martin, Carrie A. Browning-Large, Donald E. Schmechel, Kathleen A. Welsh-Bohmer, P. Murali Doraiswamy, John R. Gilbert, Jonathan L. Haines, Margaret A. Pericak-Vance

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Previous linkage studies have suggested that chromosome 12 may harbor susceptibility genes for late-onset Alzheimer disease (LOAD). No risk genes on chromosome 12 have been conclusively identified yet. We have reported that the linkage evidence for LOAD in a 12q region was significantly increased in autopsy-confirmed families particularly for those showing no linkage to alpha-T catenin gene, a LOAD candidate gene on chromosome 10 [LOD score increased from 0.1 in the autopsy-confirmed subset to 4.19 in the unlinked subset (optimal subset); p<0.0001 for the increase in LOD score], indicating a one-LOD support interval spanning 6 Mb. To further investigate this finding and to identify potential candidate LOAD risk genes for follow-up analysis, we analyzed 99 single nucleotide polymorphisms in this region, for the overall sample, the autopsy-confirmed subset, and the optimal subset, respectively, for comparison. We saw no significant association (p<0.01) in the overall sample. In the autopsy-confirmed subset, the best finding was obtained in the activation transcription factor 7 (ATF7) gene (single-locus association, p=0.002; haplotype association global, p=0.007). In the optimal subset, the best finding was obtained in the hypothetical protein FLJ20436 (FLJ20436) gene (single-locus association, p=0.0026). These results suggest that subset and covariate analyses may be one approach to help identify novel susceptibility genes on chromosome 12q for LOAD.

Original languageEnglish (US)
Pages (from-to)157-165
Number of pages9
JournalNeurogenetics
Volume7
Issue number3
DOIs
StatePublished - Jul 2006

Keywords

  • Alzheimer disease
  • APOE
  • Association study
  • Haplotype
  • SNPs

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)

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    Lin, P. I., Martin, E. R., Browning-Large, C. A., Schmechel, D. E., Welsh-Bohmer, K. A., Doraiswamy, P. M., Gilbert, J. R., Haines, J. L., & Pericak-Vance, M. A. (2006). Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis. Neurogenetics, 7(3), 157-165. https://doi.org/10.1007/s10048-006-0047-z