title: Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease.
abstract: Replications of the association between APOE-ε4 allele load and regional brain atrophy in Alzheimer's disease (AD) patients hold promise for future studies testing relationships between other disease risk gene variants and brain structure. A polymorphism, rs10868366, in the Golgi phosphoprotein 2 gene, GOLM1, was recently identified as an AD risk factor in a genome-wide association study. In a subset of the same AD cohort, we used voxel-based morphometry to test for association between the disease risk genotype and reduced regional gray matter (GM) volume in AD patients (n = 72). A mean 14% reduction in GM volume was observed in the left frontal gyrus with the higher risk GG genotype. A similar association was observed in an independent, dataset of nondemented subjects (n = 278), although with a smaller effect (1%). This replicated association with GM structural variation suggests that GOLM1 polymorphisms may be related to cognitive phenotypes. The greater effect size in AD patients also suggests that the GG genotype could be a risk factor for the expression of cognitive deficits in AD.
authors.affiliation: GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, London, United Kingdom. b.inkster@imperial.ac.uk
authors.forename: Becky
authors.initials: B
authors.lastname: Inkster
authors.forename: Anil W
authors.initials: AW
authors.lastname: Rao
authors.forename: Khanum
authors.initials: K
authors.lastname: Ridler
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
authors.forename: Brandon
authors.initials: B
authors.lastname: Whitcher
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nichols
authors.forename: Sally
authors.initials: S
authors.lastname: Wetten
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Gibson
authors.forename: Michael
authors.initials: M
authors.lastname: Borrie
authors.forename: Andrew
authors.initials: A
authors.lastname: Kertesz
authors.forename: Danilo A
authors.initials: DA
authors.lastname: Guzman
authors.forename: Inge
authors.initials: I
authors.lastname: Loy-English
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Philipp G
authors.initials: PG
authors.lastname: Saemann
authors.forename: Dorothee P
authors.initials: DP
authors.lastname: Auer
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Emilio
authors.initials: E
authors.lastname: Merlo-Pich
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D001284:Atrophy / Q000235:genetics / Q000473:pathology; D060825:Cognitive Dysfunction / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: C410824:GOLM1 protein, human; D008565:Membrane Proteins