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

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 worldwi... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America May 4, 2010, Vol.107(18), pp.8404-8409
Main Author: Ho, April J
Other Authors: 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 , Ho, April J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.0910878107
Link: http://search.proquest.com/docview/733182184/?pq-origsite=primo
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title: A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.
format: Article
creator:
  • 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
  • Ho, April J
subjects:
  • Aged–Anatomy & Histology
  • Alleles–Metabolism
  • Alpha-Ketoglutarate-Dependent Dioxygenase Fto–Genetics
  • Brain–Genetics
  • Genetic Predisposition to Disease–Genetics
  • Humans–Genetics
  • Imaging, Three-Dimensional–Genetics
  • Magnetic Resonance Imaging–Genetics
  • Obesity–Genetics
  • Organ Size–Genetics
  • Proteins–Genetics
  • Risk Factors–Genetics
  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase Fto
  • Fto Protein, Human
ispartof: Proceedings of the National Academy of Sciences of the United States of America, May 4, 2010, Vol.107(18), pp.8404-8409
description: 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. 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 ~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. Alzheimer's Disease Neuroimaging Initiative | body mass index | brain structure | tensor-based morphometry | obesity doi/ 10.1073/pnas.0910878107
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.0910878107
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleA commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.
creatorHo, 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 ; Ho, April J
contributorWeiner, Michael (correspondence author) ; Thal, Leon (record owner) ; 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 ; Korecka, Magdalena ; Toga, Arthur ; 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, 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 ; Issacson, 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, Curtis A ; Hardy, Peter ; Dekosky, Steven T ; Oakley, Mary Ann ; 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 ; Van Dyck, Christopher H ; Macavoy, Martha G ; Bifano, Laurel G ; 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 ; Wilks, Kerri L ; Wilks, Kerri L
ispartofProceedings of the National Academy of Sciences of the United States of America, May 4, 2010, Vol.107(18), pp.8404-8409
identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.0910878107
subjectAged–Anatomy & Histology ; Alleles–Metabolism ; Alpha-Ketoglutarate-Dependent Dioxygenase Fto–Genetics ; Brain–Genetics ; Genetic Predisposition to Disease–Genetics ; Humans–Genetics ; Imaging, Three-Dimensional–Genetics ; Magnetic Resonance Imaging–Genetics ; Obesity–Genetics ; Organ Size–Genetics ; Proteins–Genetics ; Risk Factors–Genetics ; Proteins ; Alpha-Ketoglutarate-Dependent Dioxygenase Fto ; Fto Protein, Human
languageeng
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descriptionA 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. 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 ~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. Alzheimer's Disease Neuroimaging Initiative | body mass index | brain structure | tensor-based morphometry | obesity doi/ 10.1073/pnas.0910878107
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15Allen, April N
16Corneveaux, Jason J
17Stephan, Dietrich A
18Decarli, Charles S
19Dechairo, Bryan M
20Potkin, Steven G
21Jack, Clifford R
22Weiner, Michael W
23Raji, Cyrus A
24Lopez, Oscar L
25Becker, James T
26Carmichael, Owen T
27Thompson, Paul M
titleA commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.
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2Alpha-Ketoglutarate-Dependent Dioxygenase Fto–Genetics
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12Anders, Dale
13Bernstein, Matthew
14Felmlee, Joel
15Fox, Nick
16Thompson, Paul
17Schuff, Norbert
18Alexander, Gene
19Bandy, Dan
20Koeppe, Robert A
21Foster, Norm
22Reiman, Eric M
23Chen, Kewei
24Shaw, Les
25Lee, Virginia
26Korecka, Magdalena
27Toga, Arthur
28Crawford, Karen
29Neu, Scott
30Harvey, Danielle
31Kornak, John
32Kachaturian, Zaven
33Frank, Richard
34Snyder, Peter J
35Molchan, Susan
36Kaye, Jeffrey
37Vorobik, Remi
38Quinn, Joseph
39Schneider, Lon
40Pawluczyk, Sonia
41Spann, Bryan
42Fleisher, Adam S
43Vanderswag, Helen
44Heidebrink, Judith L
45Lord, Joanne L
46Johnson, Kris
47Doody, Rachelle S
48Villanueva, Javier
49Chowdhury, Munir
50Stern, Yaakov
51Honig, Lawrence S
52Bell, Karen L
53Morris, John C
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55Schneider, Stacy
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59Grossman, Hillel
60Tang, Cheuk
61Stern, Jessica
62Detoledo-Morrell, Leyla
63Shah, Raj C
64Bach, Julie
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titleA commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.
authorHo, 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...
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4Genetic Predisposition to Disease–Genetics
5Humans–Genetics
6Imaging, Three-Dimensional–Genetics
7Magnetic Resonance Imaging–Genetics...
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1Stein, Jason L
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5Leow, Alex D
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7Toga, Arthur W
8Saykin, Andrew J
9Shen, Li
10Foroud, Tatiana
11Pankratz, Nathan
12Huentelman, Matthew J
13Craig, David W
14Gerber, Jill D
15Allen, April N
16Corneveaux, Jason J
17Stephan, Dietrich A
18Decarli, Charles S
19Dechairo, Bryan M
20Potkin, Steven G
21Jack, Clifford R
22Weiner, Michael W
23Raji, Cyrus A
24Lopez, Oscar L
25Becker, James T
26Carmichael, Owen T
27Thompson, Paul M
28Weiner, Michael
29Thal, Leon
30Petersen, Ronald
31Jagust, William
32Trojanowki, John
33Beckett, Laurel
34Green, Robert C
35Gamst, Anthony
36Potter, William Z
37Montine, Tom
38Anders, Dale
39Bernstein, Matthew
40Felmlee, Joel
41Fox, Nick
42Thompson, Paul
43Schuff, Norbert
44Alexander, Gene
45Bandy, Dan
46Koeppe, Robert A
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49Chen, Kewei
50Shaw, Les
51Lee, Virginia
52Korecka, Magdalena
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55Neu, Scott
56Harvey, Danielle
57Kornak, John
58Kachaturian, Zaven
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62Kaye, Jeffrey
63Vorobik, Remi
64Quinn, Joseph
65Schneider, Lon
66Pawluczyk, Sonia
67Spann, Bryan
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71Lord, Joanne L
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95Pedroso, Julia
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61Stern, Jessica
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63Shah, Raj C
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71Rusinek, Henry
72de Leon, Mony J
73De Santi, Susan M
74Doraiswamy, P Murali
75Petrella, Jeffrey R
76Aiello, Marilyn
77Clark, Christopher M
78Pham, Cassie
79Nunez, Jessica
80Smith, Charles D
81Given, Curtis A
82Hardy, Peter
83DeKosky, Steven T
84Oakley, Mary Ann
85Simpson, Donna M
86Ismail, M Saleem
87Porsteinsson, Anton
88McCallum, Colleen
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90Mulnard, Ruth A
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92Diaz-Arrastia, Ramon
93Martin-Cook, Kristen
94DeVous, Michael
95Levey, Allan I
96Lah, James J
97Cellar, Janet S
98Burns, Jeffrey M
99Anderson, Heather S
100...
atitleA commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly.
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date2010-05-04