Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins

Derrek P. Hibar, Neda Jahanshad, Jason L. Stein, Omid Kohannim, Arthur W. Toga, Sarah E. Medland, Narelle K. Hansell, Katie L. McMahon, Greig I. De Zubicaray, Grant W. Montgomery, Nicholas G. Martin, Margaret J. Wright, Paul M. Thompson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)286-295
Number of pages10
JournalTwin Research and Human Genetics
Volume15
Issue number3
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • Alzheimer's disease
  • GAB2
  • Imaging genetics
  • Tensor-based morphometry

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