Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease.
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.
Inkster
Becky
B
GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, London, United Kingdom. b.inkster@imperial.ac.uk
Rao
Anil W
AW
Ridler
Khanum
K
Filippini
Nicola
N
Whitcher
Brandon
B
Nichols
Thomas E
TE
Wetten
Sally
S
Gibson
Rachel A
RA
Borrie
Michael
M
Kertesz
Andrew
A
Guzman
Danilo A
DA
Loy-English
Inge
I
Williams
Julie
J
Saemann
Philipp G
PG
Auer
Dorothee P
DP
Holsboer
Florian
F
Tozzi
Federica
F
Muglia
Pierandrea
P
Merlo-Pich
Emilio
E
Matthews
Paul M
PM
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
C410824:GOLM1 protein, human; D008565:Membrane Proteins