Obesity and the brain: a possible genetic link

Genes play a crucial role in controlling phenotypic variability of essentially all aspects of life, including susceptibility to disease. A better understanding of the genetic factors affecting the development and function of the central nervous system, especially the human brain, are of particular interest owing to the increasing prevalence of neurodegenerative disorders such as Alzheimer's disease (AD).Investigators from the Alzheimer's Disease Neuroimaging Initiative (ADNI) - a research project aimed at studying the rate of change of cognition, brain structure and function, and biomarkers in large collections of both cognitively healthy and impaired subjects - recently published data suggesting a possible connection between certain common genetic variants and brain volume in ~200 healthy older subjects [1]. Specifically, the authors tested the hypothesis of whether or not specific alleles in the gene encoding the fat mass and obesity-associated protein (FTO), located on chromosome 16q12.2, correlate with regional brain volumes as determined by magnetic resonance imaging.This question arose because the same FTO alleles at - highly correlated - SNPs were previously found to show association with elevated body mass index (BMI), a commonly used surrogate measure of adiposity [2-5]. Elevated BMI itself has been reported to correlate with structural brain deficits - in particular, frontal, temporal, and subcortical atrophy [6] - but no study had previously assessed whether this correlation was driven by genetic variation in the FTO gene.The new data from the ADNI group show that, indeed, the same common SNPs associated with BMI are also associated with a ~10% reduction in brain volume in the frontal and occipital lobes, while elevated BMI alone was associated with relatively broadly distributed brain atrophy in the frontal, temporal, parietal and occipital lobes [1]. As expected, the FTO association was highly correlated with the overall effect of BMI on brain volume, b