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

Publication ,  Journal Article
Lin, P-I; Martin, ER; Browning-Large, CA; Schmechel, DE; Welsh-Bohmer, KA; Doraiswamy, PM; Gilbert, JR; Haines, JL; Pericak-Vance, MA
Published in: Neurogenetics
July 2006

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.

Duke Scholars

Published In

Neurogenetics

DOI

ISSN

1364-6745

Publication Date

July 2006

Volume

7

Issue

3

Start / End Page

157 / 165

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genetic Testing
  • Genetic Predisposition to Disease
  • Genetic Linkage
  • Genetic Heterogeneity
  • Chromosomes, Human, Pair 12
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lin, P.-I., Martin, E. R., Browning-Large, C. A., Schmechel, D. E., Welsh-Bohmer, K. A., Doraiswamy, P. M., … 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
Lin, Ping-I, Eden R. Martin, Carrie A. Browning-Large, Donald E. Schmechel, Kathleen A. Welsh-Bohmer, P Murali Doraiswamy, John R. Gilbert, Jonathan L. Haines, and Margaret A. Pericak-Vance. “Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis.Neurogenetics 7, no. 3 (July 2006): 157–65. https://doi.org/10.1007/s10048-006-0047-z.
Lin P-I, Martin ER, Browning-Large CA, Schmechel DE, Welsh-Bohmer KA, Doraiswamy PM, et al. Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis. Neurogenetics. 2006 Jul;7(3):157–65.
Lin, Ping-I., et al. “Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis.Neurogenetics, vol. 7, no. 3, July 2006, pp. 157–65. Pubmed, doi:10.1007/s10048-006-0047-z.
Lin P-I, Martin ER, Browning-Large CA, Schmechel DE, Welsh-Bohmer KA, Doraiswamy PM, Gilbert JR, Haines JL, Pericak-Vance MA. Parsing the genetic heterogeneity of chromosome 12q susceptibility genes for Alzheimer disease by family-based association analysis. Neurogenetics. 2006 Jul;7(3):157–165.
Journal cover image

Published In

Neurogenetics

DOI

ISSN

1364-6745

Publication Date

July 2006

Volume

7

Issue

3

Start / End Page

157 / 165

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Neurology & Neurosurgery
  • Linkage Disequilibrium
  • Humans
  • Haplotypes
  • Genetic Testing
  • Genetic Predisposition to Disease
  • Genetic Linkage
  • Genetic Heterogeneity
  • Chromosomes, Human, Pair 12