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

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Neurogenetics : Volume 7, Issue 2, May 2006

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

Content Provider	Springer Nature Link
Author	Lin, Ping I Martin, Eden R. Browning Large, Carrie A. Schmechel, Donald E. Welsh Bohmer, Kathleen A. Doraiswamy, P. Murali Gilbert, John R. Haines, Jonathan L. Pericak Vance, Margaret A.
Copyright Year	2006
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.
Starting Page	157
Ending Page	165
Page Count	9
File Format	PDF
ISSN	13646745
Journal	Neurogenetics
Volume Number	7
Issue Number	3
e-ISSN	13646753
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-06-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Alzheimer disease APOE Association study SNPs Haplotype Neurosciences Molecular Medicine Human Genetics
Content Type	Text
Resource Type	Article
Subject	Genetics Cellular and Molecular Neuroscience Genetics (clinical)

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