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Proc Natl Acad Sci U S A. 2010 May 4;107(18):8404-9. doi: 10.1073/pnas.0910878107. Epub 2010 Apr 19.

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

Collaborators (194)

Weiner M, Thal L, Petersen R, Jack CR, Jagust W, Trojanowki J, Toga AW, Beckett L, Green RC, Gamst A, Potter WZ, Montine T, Anders D, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, Bandy D, Koeppe RA, Foster N, Reiman EM, Chen K, Trojanowki J, Shaw L, Lee V, Korecka M, Toga A, Crawford K, Neu S, Harvey D, Gamst A, Kornak J, Kachaturian Z, Frank R, Snyder PJ, Molchan S, Kaye J, Vorobik R, Quinn J, Schneider L, Pawluczyk S, Spann B, Fleisher AS, Vanderswag H, Heidebrink JL, Lord JL, Johnson K, Doody RS, Villanueva J, Chowdhury M, Stern Y, Honig LS, Bell KL, Morris JC, Mintun MA, Schneider S, Marson D, Griffith R, Badger B, Grossman H, Tang C, Stern J, deToledo-Morrell L, Shah RC, Bach J, Duara R, Issacson R, Strauman S, Albert MS, Pedroso J, Toroney J, Rusinek H, de Leon MJ, De Santi SM, Doraiswamy PM, Petrella JR, Aiello M, Clark CM, Pham C, Nunez J, Smith CD, Given CA 2nd, Hardy P, DeKosky ST, Oakley MA, Simpson DM, Ismail MS, Porsteinsson A, McCallum C, Cramer SC, Mulnard RA, McAdams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey AI, Lah JJ, Cellar JS, Burns JM, Anderson HS, Laubinger MM, Bartzokis G, Silverman DH, Lu PH, Fletcher R, Parfitt F, Johnson H, Farlow M, Herring S, Hake A, Van Dyck CH, MacAvoy MG, Bifano LG, Chertkow H, Bergman H, Hosein C, Black S, Graham S, Caldwell C, Feldman H, Assaly M, Hsiung GY, Kertesz A, Rogers J, Trost D, Bernick C, Gitelman D, Johnson N, Mesulam M, Sadowsky C, Villena T, Mesner S, Aisen PS, Johnson KB, Behan KE, Sperling RA, Rentz DM, Johnson KA, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Obradov S, Killiany R, Norbash A, Obisesan TO, Jayam-Trouth A, Wang P, Auchus AP, Huang J, Friedland RP, DeCarli C, Fletcher E, Carmichael O, Kittur S, Mirje S, Johnson SC, Borrie M, Lee T-, Asthana S, Carlsson CM, Potkin SG, Highum D, Preda A, Nguyen D, Tariot PN, Hendin BA, Scharre DW, Kataki M, Beversdorf DQ, Zimmerman EA, Celmins D, Brown AD, Gandy S, Marenberg ME, Rovner BW, Pearlson G, Blank K, Anderson K, Saykin AJ, Santulli RB, Pare N, Williamson JD, Sink KM, Potter H, Ashok Raj B, Giordano A, Ott BR, Wu CK, Cohen R, Wilks KL.

Abstract

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an approximately 1.2 kg higher weight, on average, in adults and an approximately 1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to 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 scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of approximately 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 attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

PMID:
20404173
[PubMed - indexed for MEDLINE]
PMCID:
PMC2889537
Free PMC Article
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