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

2010; National Academy of Sciences; Volume: 107; Issue: 18 Linguagem: Inglês

10.1073/pnas.0910878107

1091-6490

April J. Ho, Jason L. Stein, Xue Hua, Suh Lee, Derrek P. Hibar, Alex Leow, Ivo D. Dinov, Arthur W. Toga, Andrew J. Saykin, Li Shen, Tatiana Foroud, Nathan Pankratz, Matthew J. Huentelman, David W. Craig, Jill D. Gerber, April N. Allen, Jason J. Corneveaux, Dietrich A. Stephan, Charles DeCarli, Bryan Dechairo, Steven G. Potkin, Clifford R. Jack, Michael W. Weiner, Cyrus A. Raji, Oscar L. López, James T. Becker, Owen Carmichael, Paul M. Thompson, Michael W. Weiner, Leon J. Thal, Ronald C. Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Anthony Gamst, William Z. Potter, Tom Montine, Dale Anders, Matt A. Bernstein, Joel P. Felmlee, Nick C. Fox, Paul M. Thompson, Norbert Schuff, Gene E. Alexander, Dan Bandy, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, John Q. Trojanowki, Les Shaw, Virginia M.‐Y. Lee, Magdalena Korecka, Arthur W. Toga, Karen Crawford, Scott Neu, Danielle Harvey, Anthony Gamst, John Kornak, Zaven Kachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Remi Vorobik, Joseph F. Quinn, Lon S. Schneider, Sonia Pawluczyk, Bryan Spann, Adam Fleisher, Helen Vanderswag, Judith L. Heidebrink, Joanne Lord, Kris Johnson, Rachelle S. Doody, Javier Villanueva‐Meyer, Munir Chowdhury, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, John C. Morris, Mark A. Mintun, Stacy Schneider, Daniel Marson, Randall Griffith, Beverly Badger, Hillel Grossman, Cheuk Y. Tang, Jessica Stern, Leyla deToledo‐Morrell, Raj C. Shah, Julie Bach, Ranjan Duara, Richard Isaacson, Silvia Strauman, Marilyn S. Albert, Julia Pedroso, Jaimie Toroney, Henry Rusinek, Mony J. de Leon, Susan M De Santi, P. Murali Doraiswamy, Jeffrey R. Petrella, Marilyn Aiello, Christopher M. Clark, Cassie Pham, Jessica Nuñez, Charles D. Smith, Curtis A. Given, Peter Hardy, Steven T. DeKosky, MaryAnn Oakley, Donna M. Simpson, M. Saleem Ismail, Anton P. Porsteinsson, Colleen McCallum, Steven C. Cramer, Ruth A. Mulnard, Catherine Mc-Adams-Ortiz, Ramon Diaz‐Arrastia, Kristen Martin-Cook, Michael D. Devous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Heather S. Anderson, Mary M. Laubinger, George Bartzokis, Daniel Silverman, Po H. Lu, Rita Fletcher, Francine Parfitt, Heather Johnson, Martin R. Farlow, Scott Herring, Ann Marie Hake, Christopher H. van Dyck, Martha G. MacAvoy, Laurel A. Bifano, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra E. Black, Simon J. Graham, Curtis Caldwell, Howard Feldman, Michele Assaly, Ging‐Yuek Robin Hsiung, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Darren R. Gitelman, Nancy Johnson, Marsel Mesulam, Carl Sadowsky, Teresa Villena, Scott Mesner, Paul Aisen, Kathleen Johnson, Kelly E. Behan, Reisa A. Sperling, Dorene M. Rentz, Keith A. Johnson, Allyson Rosen, Jared Tinklenberg, Wes Ashford, Marwan N. Sabbagh, Donald J. Connor, Sanja Obradov, Ronald Killiany, Alexander Norbash, Thomas O. Obisesan, Annapurni Jayam‐Trouth, Paul J. Wang, Alexander P. Auchus, Juebin Huang, Robert P. Friedland, Charles DeCarli, Evan Fletcher, Owen Carmichael, Smita Kittur, Seema Mirje, Sterling C. Johnson, Michael Borrie, T‐Y Lee, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Diane Highum, Adrian Preda, Dana Nguyen, Pierre N. Tariot, Barry Hendin, Douglas W. Scharre, Maria Kataki, David Q. Beversdorf, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Sam Gandy, Marjorie E. Marenberg, Barry W. Rovner, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Andrew J. Saykin, Robert B. Santulli, Nadia Paré, Jeff D. Williamson, Kaycee M. Sink, Huntington Potter, Balebail Ashok Raj, Amy T. Giordano, Brian R. Ott, Chuang‐Kuo Wu, Ronald A. Cohen, Kerri Wilks,

Diabetes Treatment and Management

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.