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Human Mutation
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Human Mutation
Article . 2008 . Peer-reviewed
License: Wiley TDM
Data sources: Crossref
Human Mutation
Article . 2009
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Genomic convergence to identify candidate genes for Alzheimer Disease on chromosome 10

Authors: Xueying, Liang; Michael, Slifer; Eden R, Martin; Nathalie, Schnetz-Boutaud; Jackie, Bartlett; Brent, Anderson; Stephan, Züchner; +4 Authors

Genomic convergence to identify candidate genes for Alzheimer Disease on chromosome 10

Abstract

A broad region of chromosome 10 (chr10) has engendered continued interest in the etiology of late-onset Alzheimer Disease (LOAD) from both linkage and candidate gene studies. However, there is a very extensive heterogeneity on chr10. We converged linkage analysis and gene expression data using the concept of genomic convergence that suggests that genes showing positive results across multiple different data types are more likely to be involved in AD. We identified and examined 28 genes on chr10 for association with AD in a Caucasian case-control dataset of 506 cases and 558 controls with substantial clinical information. The cases were all LOAD (minimum age at onset > or = 60 years). Both single marker and haplotypic associations were tested in the overall dataset and 8 subsets defined by age, gender, ApoE and clinical status. PTPLA showed allelic, genotypic and haplotypic association in the overall dataset. SORCS1 was significant in the overall data sets (p=0.0025) and most significant in the female subset (allelic association p=0.00002, a 3-locus haplotype had p=0.0005). Odds Ratio of SORCS1 in the female subset was 1.7 (p<0.0001). SORCS1 is an interesting candidate gene involved in the Abeta pathway. Therefore, genetic variations in PTPLA and SORCS1 may be associated and have modest effect to the risk of AD by affecting Abeta pathway. The replication of the effect of these genes in different study populations and search for susceptible variants and functional studies of these genes are necessary to get a better understanding of the roles of the genes in Alzheimer disease.

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Keywords

Aged, 80 and over, Family Health, Male, Calcium Channels, L-Type, Genotype, Chromosomes, Human, Pair 10, Chromosome Mapping, Epistasis, Genetic, Middle Aged, Models, Biological, Genetic Heterogeneity, Logistic Models, Gene Frequency, Haplotypes, Alzheimer Disease, Humans, Female, Genetic Predisposition to Disease, Lod Score, Aged

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    73
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
73
Top 10%
Top 10%
Top 10%
bronze