title: Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins.
abstract: The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27-1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.
authors.affiliation: Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.forename: Neda
authors.initials: N
authors.lastname: Jahanshad
authors.forename: Jason L
authors.initials: JL
authors.lastname: Stein
authors.forename: Omid
authors.initials: O
authors.lastname: Kohannim
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.forename: Narelle K
authors.initials: NK
authors.lastname: Hansell
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human