A commonly carried allele of the obesity-relatedFTOgene is associated with reduced brain volume in the healthy elderly
Authors: Ho April J. , Stein Jason L. , Hua Xue , Lee Suh , Hibar Derrek P. , Leow Alex D. , Dinov Ivo D. , Toga Arthur W. , Saykin Andrew J. , Shen Li , Foroud Tatiana , Pankratz Nathan , Huentelman Matthew J. , Craig David W. , Gerber Jill D. , Allen April N. , Corneveaux Jason J. , Stephan Dietrich A. , DeCarli Charles S. , DeChairo Bryan M. , Potkin Steven G. , Jack Clifford R. , Weiner Michael W. , Raji Cyrus A. , Lopez Oscar L. , Becker James T. , Carmichael Owen T. , Thompson Paul M. ,   the Alzheimer's Disease Neuroimaging Initiative, Weiner Michael , Thal Leon , Petersen Ronald , Jack Clifford R. , Jagust William , Trojanowki John , Toga Arthur W. , Beckett Laurel , Green Robert C. , Gamst Anthony , Potter William Z. , Montine Tom , Anders Dale , Bernstein Matthew , Felmlee Joel , Fox Nick , Thompson Paul , Schuff Norbert , Alexander Gene , Bandy Dan , Koeppe Robert A. , Foster Norm , Reiman Eric M. , Chen Kewei , Trojanowki John , Shaw Les , Lee Virginia M.-Y. , Korecka Magdalena , Toga Arthur W. , Crawford Karen , Neu Scott , Harvey Danielle , Gamst Anthony , Kornak John , Kachaturian Zaven , Frank Richard , Snyder Peter J. , Molchan Susan , Kaye Jeffrey , Vorobik Remi , Quinn Joseph , Schneider Lon , Pawluczyk Sonia , Spann Bryan , Fleisher Adam S. , Vanderswag Helen , Heidebrink Judith L. , Lord Joanne L. , Johnson Kris , Doody Rachelle S. , Villanueva-Meyer Javier , Chowdhury Munir , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Morris John C. , Mintun Mark A. , Schneider Stacy , Marson Daniel , Griffith Randall , Badger Beverly , Grossman Hillel , Tang Cheuk , Stern Jessica , deToledo-Morrell Leyla , Shah Raj C. , Bach Julie , Duara Ranjan , Isaacson Richard , Strauman Silvia , Albert Marilyn S. , Pedroso Julia , Toroney Jaimie , Rusinek Henry , de Leon Mony J , De Santi Susan M , Doraiswamy P. Murali , Petrella Jeffrey R. , Aiello Marilyn , Clark Christopher M. , Pham Cassie , Nunez Jessica , Smith Charles D. , Given II Curtis A. , Hardy Peter , DeKosky Steven T. , Oakley MaryAnn , Simpson Donna M. , Ismail M. Saleem , Porsteinsson Anton , McCallum Colleen , Cramer Steven C. , Mulnard Ruth A. , McAdams-Ortiz Catherine , Diaz-Arrastia Ramon , Martin-Cook Kristen , DeVous Michael , Levey Allan I. , Lah James J. , Cellar Janet S. , Burns Jeffrey M. , Anderson Heather S. , Laubinger Mary M. , Bartzokis George , Silverman Daniel H.S. , Lu Po H. , Fletcher Rita , Parfitt Francine , Johnson Heather , Farlow Martin , Herring Scott , Hake Ann M. , van Dyck Christopher H. , MacAvoy Martha G. , Bifano Laurel A. , Chertkow Howard , Bergman Howard , Hosein Chris , Black Sandra , Graham Simon , Caldwell Curtis , Feldman Howard , Assaly Michele , Hsiung Ging-Yuek R. , Kertesz Andrew , Rogers John , Trost Dick , Bernick Charles , Gitelman Darren , Johnson Nancy , Mesulam Marsel , Sadowsky Carl , Villena Teresa , Mesner Scott , Aisen Paul S. , Johnson Kathleen B. , Behan Kelly E. , Sperling Reisa A. , Rentz Dorene M. , Johnson Keith A. , Rosen Allyson , Tinklenberg Jared , Ashford Wes , Sabbagh Marwan , Connor Donald , Obradov Sanja , Killiany Ron , Norbash Alex , Obisesan Thomas O. , Jayam-Trouth Annapurni , Wang Paul , Auchus Alexander P. , Huang Juebin , Friedland Robert P. , DeCarli Charles , Fletcher Evan , Carmichael Owen , Kittur Smita , Mirje Seema , Johnson Sterling C. , Borrie Michael , Lee T-Y , Asthana Sanjay , Carlsson Cynthia M. , Potkin Steven G. , Highum Diane , Preda Adrian , Nguyen Dana , Tariot Pierre N. , Hendin Barry A. , Scharre Douglas W. , Kataki Maria , Beversdorf David Q. , Zimmerman Earl A. , Celmins Dzintra , Brown Alice D. , Gandy Sam , Marenberg Marjorie E. , Rovner Barry W. , Pearlson Godfrey , Blank Karen , Anderson Karen , Saykin Andrew J. , Santulli Robert B. , Pare Nadia , Williamson Jeff D. , Sink Kaycee M. , Potter Huntington , Ashok Raj B. , Giordano Amy , Ott Brian R. , Wu Chuang-Kuo , Cohen Ronald , Wilks Kerri L. 
Published: April 2010

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 ~1.2 kg higher weight, on average, in adults and an ~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.FTOis 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,FTOrisk allele carriers versus noncarriers had an average brain volume 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 attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher inFTOrisk 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.