title: 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.
authors.affiliation: Celera Diagnostics, Alameda, CA 94502, USA.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Li
authors.forename: Petra
authors.initials: P
authors.lastname: Nowotny
authors.forename: Peter
authors.initials: P
authors.lastname: Holmans
authors.forename: Scott
authors.initials: S
authors.lastname: Smemo
authors.forename: John S K
authors.initials: JS
authors.lastname: Kauwe
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Hinrichs
authors.forename: Kristina
authors.initials: K
authors.lastname: Tacey
authors.forename: Lisa
authors.initials: L
authors.lastname: Doil
authors.forename: Ryan
authors.initials: R
authors.lastname: van Luchene
authors.forename: Veronica
authors.initials: V
authors.lastname: Garcia
authors.forename: Charles
authors.initials: C
authors.lastname: Rowland
authors.forename: Steve
authors.initials: S
authors.lastname: Schrodi
authors.forename: Diane
authors.initials: D
authors.lastname: Leong
authors.forename: Goran
authors.initials: G
authors.lastname: Gogic
authors.forename: Joanne
authors.initials: J
authors.lastname: Chan
authors.forename: Anibal
authors.initials: A
authors.lastname: Cravchik
authors.forename: David
authors.initials: D
authors.lastname: Ross
authors.forename: Kit
authors.initials: K
authors.lastname: Lau
authors.forename: Shirley
authors.initials: S
authors.lastname: Kwok
authors.forename: Sheng-Yung
authors.initials: SY
authors.lastname: Chang
authors.forename: Joe
authors.initials: J
authors.lastname: Catanese
authors.forename: John
authors.initials: J
authors.lastname: Sninsky
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: White
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Leon
authors.initials: L
authors.lastname: Thal
authors.forename: Michael
authors.initials: M
authors.lastname: Owen
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Andrew
authors.initials: A
authors.lastname: Grupe
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D001921:Brain / Q000201:enzymology; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D015870:Gene Expression; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D009410:Nerve Degeneration; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases