Twin Research and Human Genetics


Alzheimer's Disease Risk Gene, GAB2, is Associated with Regional Brain Volume Differences in 755 Young Healthy Twins

Derrek P. Hibara1, Neda Jahanshada1, Jason L. Steina1, Omid Kohannima1, Arthur W. Togaa1, Sarah E. Medlanda2a3a4, Narelle K. Hansella2, Katie L. McMahona5, Greig I. de Zubicaraya6, Grant W. Montgomerya2, Nicholas G. Martina2, Margaret J. Wrighta2 and Paul M. Thompsona1 c1

a1 Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, USA

a2 Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia

a3 Quantitative Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, Australia

a4 Broad Institute of Harvard and MIT, Boston, USA

a5 Centre for Advanced Imaging, University of Queensland, Brisbane, Australia

a6 Functional Magnetic Resonance Imaging Laboratory, School of Psychology, University of Queensland, Brisbane, Australia


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.

(Received February 01 2012)

(Accepted March 26 2012)


  • GAB2;
  • imaging genetics;
  • tensor-based morphometry;
  • Alzheimer's disease


c1 address for correspondence: Dr Paul Thompson, Professor of Neurology, Laboratory of Neuro Imaging, Dept. of Neurology, UCLA School of Medicine, Neuroscience Research Building 225E, 635 Charles Young Drive, Los Angeles, CA 90095-1769, USA. E-mail: