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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lin, P-I; Martin, ER; Browning-Large, CA; Schmechel, DE; Welsh-Bohmer, KA; Doraiswamy, PM; Gilbert, JR; Haines, JL; Pericak-Vance, MA

Published Date

  • July 2006

Published In

Volume / Issue

  • 7 / 3

Start / End Page

  • 157 - 165

PubMed ID

  • 16770605

Pubmed Central ID

  • 16770605

International Standard Serial Number (ISSN)

  • 1364-6745

Digital Object Identifier (DOI)

  • 10.1007/s10048-006-0047-z

Language

  • eng

Conference Location

  • United States