A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

m Radiology, n Epidemiology, o Psychiatry, p Psychology, q understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scannedwithMRIandgenotypedaspartoftheAlzheimer'sDisease Neuroimaging Initiative. We found a pattern of systematic brain volumedeficitsincarriersoftheobesity-associatedriskalleleversus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain vol- ume difference of ∼8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attrib- utable to differences in cholesterol levels, hypertension, or the vol- ume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain mapsrevealthatacommonlycarriedsusceptibilityalleleforobesity isassociatedwithstructuralbrainatrophy,withimplicationsforthe health of the elderly.