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Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family.


ABSTRACT: Although several genes have been implicated in the development of the early-onset autosomal dominant form of Alzheimer's disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-control series totaling 1,089 LOAD patients and 1,196 control subjects and report association with SNPs in the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene. Subsequent analysis of GAPD paralogs on other chromosomes demonstrated association with two other paralogs. A significant association between LOAD and a compound genotype of the three GAPD genes was observed in all three sample sets. Individually, these SNPs make differential contributions to disease risk in each of the casecontrol series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis.

SUBMITTER: Li Y 

PROVIDER: S-EPMC524264 | biostudies-literature | 2004 Nov

REPOSITORIES: biostudies-literature

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Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family.

Li Yonghong Y   Nowotny Petra P   Holmans Peter P   Smemo Scott S   Kauwe John S K JS   Hinrichs Anthony L AL   Tacey Kristina K   Doil Lisa L   van Luchene Ryan R   Garcia Veronica V   Rowland Charles C   Schrodi Steve S   Leong Diane D   Gogic Goran G   Chan Joanne J   Cravchik Anibal A   Ross David D   Lau Kit K   Kwok Shirley S   Chang Sheng-Yung SY   Catanese Joe J   Sninsky John J   White Thomas J TJ   Hardy John J   Powell John J   Lovestone Simon S   Morris John C JC   Thal Leon L   Owen Michael M   Williams Julie J   Goate Alison A   Grupe Andrew A  

Proceedings of the National Academy of Sciences of the United States of America 20041026 44


Although several genes have been implicated in the development of the early-onset autosomal dominant form of Alzheimer's disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-contro  ...[more]

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