Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 14 April 2006:
Vol. 312. no. 5771, pp. 279 - 283
DOI: 10.1126/science.1124779
Prev | Table of Contents | Next

Reports

A Common Genetic Variant Is Associated with Adult and Childhood Obesity

Alan Herbert,1* Norman P. Gerry,1 Matthew B. McQueen,2 Iris M. Heid,3,4 Arne Pfeufer,5,6 Thomas Illig,3,4 H.-Erich Wichmann,3,4,7 Thomas Meitinger,5,6 David Hunter,2,8,9 Frank B. Hu,2,8,9 Graham Colditz,8,9 Anke Hinney,10 Johannes Hebebrand,10 Kerstin Koberwitz,6,10 Xiaofeng Zhu,11 Richard Cooper,11 Kristin Ardlie,12 Helen Lyon,13,14,15 Joel N. Hirschhorn,13,14,15 Nan M. Laird,16 Marc E. Lenburg,1 Christoph Lange,9,13 Michael F. Christman1*

Obesity is a heritable trait and a risk factor for many common diseases such as type 2 diabetes, heart disease, and hypertension. We used a dense whole-genome scan of DNA samples from the Framingham Heart Study participants to identify a common genetic variant near the INSIG2 gene associated with obesity. We have replicated the finding in four separate samples composed of individuals of Western European ancestry, African Americans, and children. The obesity-predisposing genotype is present in 10% of individuals. Our study suggests that common genetic polymorphisms are important determinants of obesity.

1 Department of Genetics and Genomics, Boston University Medical School, E613, 715 Albany Street, Boston, MA 02118, USA.
2 Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
3 Institute of Epidemiology, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.
4 KORA Group, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.
5 Institute of Human Genetics, Forschungszentrum für Umwelt und Gesundheit, D-85764 Neuherberg, Germany.
6 Institute of Human Genetics, Technical University Munich, D-81671 Munich, Germany.
7 Institute for Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University, Munich, Germany.
8 Nurses Health Study, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
9 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
10 Department of Child and Adolescent Psychiatry of the University of Duisburg-Essen, D-45147 Essen, Germany.
11 Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL 60153, USA.
12 Genomics Collaborative, SeraCare Life Sciences, Cambridge, MA, USA.
13 Program in Genomics and Divisions of Genetics and Endocrinology, Children's Hospital, Boston, MA 02115, USA.
14 Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
15 Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.
16 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: aherbert{at}bu.edu (A.H.); mfc{at}bu.edu (M.F.C.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Adipose Tissue Expression and Genetic Variants of the Bone Morphogenetic Protein Receptor 1A Gene (BMPR1A) Are Associated With Human Obesity.
Y. Bottcher, H. Unbehauen, N. Kloting, K. Ruschke, A. Korner, D. Schleinitz, A. Tonjes, B. Enigk, S. Wolf, K. Dietrich, et al. (2009)
Diabetes 58, 2119-2128
   Abstract »    Full Text »    PDF »
Physical Therapists' Attitudes, Knowledge, and Practice Approaches Regarding People Who Are Obese.
S. Sack, D. R. Radler, K. K. Mairella, R. Touger-Decker, and H. Khan (2009)
Physical Therapy 89, 804-815
   Abstract »    Full Text »    PDF »
Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro.
M. S. Byerly, J. Simon, E. Lebihan-Duval, M. J. Duclos, L. A. Cogburn, and T. E. Porter (2009)
Am J Physiol Regulatory Integrative Comp Physiol 296, R1180-R1189
   Abstract »    Full Text »    PDF »
Estimating the number of unseen variants in the human genome.
I. Ionita-Laza, C. Lange, and N. M. Laird (2009)
PNAS 106, 5008-5013
   Abstract »    Full Text »    PDF »
From the Cover: Model of genetic variation in human social networks.
J. H. Fowler, C. T. Dawes, and N. A. Christakis (2009)
PNAS 106, 1720-1724
   Abstract »    Full Text »    PDF »
Genetic factors contributing to obesity and body weight can act through mechanisms affecting muscle weight, fat weight, or both.
G. A. Brockmann, S.-W. Tsaih, C. Neuschl, G. A. Churchill, and R. Li (2009)
Physiol Genomics 36, 114-126
   Abstract »    Full Text »    PDF »
Prevalence in the United States of Selected Candidate Gene Variants: Third National Health and Nutrition Examination Survey, 1991-1994.
M.-h. Chang, M. L. Lindegren, M. A. Butler, S. J. Chanock, N. F. Dowling, M. Gallagher, R. Moonesinghe, C. A. Moore, R. M. Ned, M. R. Reichler, et al. (2009)
Am. J. Epidemiol. 169, 54-66
   Abstract »    Full Text »    PDF »
Prevention and Treatment of Pediatric Obesity: An Endocrine Society Clinical Practice Guideline Based on Expert Opinion.
G. P. August, S. Caprio, I. Fennoy, M. Freemark, F. R. Kaufman, R. H. Lustig, J. H. Silverstein, P. W. Speiser, D. M. Styne, and V. M. Montori (2008)
J. Clin. Endocrinol. Metab. 93, 4576-4599
   Abstract »    Full Text »    PDF »
The Importance of Gene--Environment Interaction: Implications for Social Scientists.
K. E. North and L. J. Martin (2008)
Sociological Methods Research 37, 164-200
   Abstract »    PDF »
Is Obesity Our Genetic Legacy?.
A. I. F. Blakemore and P. Froguel (2008)
J. Clin. Endocrinol. Metab. 93, s51-s56
   Abstract »    Full Text »    PDF »
Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
K. L. Mohlke, M. Boehnke, and G. R. Abecasis (2008)
Hum. Mol. Genet. 17, R102-R108
   Abstract »    Full Text »    PDF »
ARG1 Is a Novel Bronchodilator Response Gene: Screening and Replication in Four Asthma Cohorts.
A. A. Litonjua, J. Lasky-Su, K. Schneiter, K. G. Tantisira, R. Lazarus, B. Klanderman, J. J. Lima, C. G. Irvin, S. P. Peters, J. P. Hanrahan, et al. (2008)
Am. J. Respir. Crit. Care Med. 178, 688-694
   Abstract »    Full Text »    PDF »
The Author Responds to "Evaluating p Values and Bayes Factors".
J. P. A. Ioannidis (2008)
Am. J. Epidemiol. 168, 389-390
   Full Text »    PDF »
Common Variation in the Fat Mass and Obesity-Associated (FTO) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population.
Y.-C. Chang, P.-H. Liu, W.-J. Lee, T.-J. Chang, Y.-D. Jiang, H.-Y. Li, S.-S. Kuo, K.-C. Lee, and L.-M. Chuang (2008)
Diabetes 57, 2245-2252
   Abstract »    Full Text »    PDF »
Association of FTO With Obesity-Related Traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort.
A. F. Marvelle, L. A. Lange, L. Qin, L. S. Adair, and K. L. Mohlke (2008)
Diabetes 57, 1987-1991
   Abstract »    Full Text »    PDF »
Microarray Technology and Applications in the Arena of Genome-Wide Association.
S. F. A. Grant and H. Hakonarson (2008)
Clin. Chem. 54, 1116-1124
   Abstract »    Full Text »    PDF »
Genome-wide association scans identified CTNNBL1 as a novel gene for obesity.
Y.-J. Liu, X.-G. Liu, L. Wang, C. Dina, H. Yan, J.-F. Liu, S. Levy, C. J. Papasian, B. M. Drees, J. J. Hamilton, et al. (2008)
Hum. Mol. Genet. 17, 1803-1813
   Abstract »    Full Text »    PDF »
R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population.
D. Meyre, M. Farge, C. Lecoeur, C. Proenca, E. Durand, F. Allegaert, J. Tichet, M. Marre, B. Balkau, J. Weill, et al. (2008)
Hum. Mol. Genet. 17, 1798-1802
   Abstract »    Full Text »    PDF »
Update on Obesity.
D. H. Bessesen (2008)
J. Clin. Endocrinol. Metab. 93, 2027-2034
   Abstract »    Full Text »    PDF »
Overweight and Obese Prevalence Rates in African American and Hispanic Children: An Analysis of Data from the 2003-2004 National Survey of Children's Health.
M. N. Lutfiyya, R. Garcia, C. M. Dankwa, T. Young, and M. S. Lipsky (2008)
J Am Board Fam Med 21, 191-199
   Abstract »    Full Text »    PDF »
National Emphysema Treatment Trial State of the Art: Genetics of Emphysema.
C. P. Hersh, D. L. DeMeo, and E. K. Silverman (2008)
Proceedings of the ATS 5, 486-493
   Abstract »    Full Text »    PDF »
Insulin-Induced Gene 2 Involvement in Human Adipocyte Metabolism and Body Weight Regulation.
S. Krapivner, S. Popov, E. Chernogubova, M.-L. Hellenius, R. M. Fisher, A. Hamsten, and F. M. van't Hooft (2008)
J. Clin. Endocrinol. Metab. 93, 1995-2001
   Abstract »    Full Text »    PDF »
Genomics: The Next Step to Elucidate the Etiology of Calcific Aortic Valve Stenosis.
Y. Bosse, P. Mathieu, and P. Pibarot (2008)
J. Am. Coll. Cardiol. 51, 1327-1336
   Abstract »    Full Text »    PDF »
Regulation of Fto/Ftm gene expression in mice and humans.
G. Stratigopoulos, S. L. Padilla, C. A. LeDuc, E. Watson, A. T. Hattersley, M. I. McCarthy, L. M. Zeltser, W. K. Chung, and R. L. Leibel (2008)
Am J Physiol Regulatory Integrative Comp Physiol 294, R1185-R1196
   Abstract »    Full Text »    PDF »
A common VLDLR polymorphism interacts with APOE genotype in the prediction of carotid artery disease risk.
D. C. Crawford, A. S. Nord, M. D. Badzioch, J. Ranchalis, L. A. McKinstry, M. Ahearn, C. Bertucci, C. Shephard, M. Wong, M. J. Rieder, et al. (2008)
J. Lipid Res. 49, 588-596
   Abstract »    Full Text »    PDF »
Association of Morbid Obesity With FTO and INSIG2 Allelic Variants.
X. Chu, R. Erdman, M. Susek, H. Gerst, K. Derr, M. Al-Agha, G. C. Wood, C. Hartman, S. Yeager, M. A. Blosky, et al. (2008)
Arch Surg 143, 235-240
   Abstract »    Full Text »    PDF »
Evidence of an Influence of a Polymorphism Near the INSIG2 on Weight Loss During a Lifestyle Intervention in Obese Children and Adolescents.
T. Reinehr, A. Hinney, T. T. Nguyen, and J. Hebebrand (2008)
Diabetes 57, 623-626
   Abstract »    Full Text »    PDF »
Identification and Replication of a Novel Obesity Locus on Chromosome 1q24 in Isolated Populations of Cilento.
M. Ciullo, T. Nutile, C. Dalmasso, R. Sorice, C. Bellenguez, V. Colonna, M. G. Persico, and C. Bourgain (2008)
Diabetes 57, 783-790
   Abstract »    Full Text »    PDF »
Assessment of cumulative evidence on genetic associations: interim guidelines.
J. P. Ioannidis, P. Boffetta, J. Little, T. R O'Brien, A. G Uitterlinden, P. Vineis, D. J Balding, A. Chokkalingam, S. M Dolan, W D. Flanders, et al. (2008)
Int. J. Epidemiol. 37, 120-132
   Abstract »    Full Text »    PDF »
Low Physical Activity Accentuates the Effect of the FTO rs9939609 Polymorphism on Body Fat Accumulation.
C. H. Andreasen, K. L. Stender-Petersen, M. S. Mogensen, S. S. Torekov, L. Wegner, G. Andersen, A. L. Nielsen, A. Albrechtsen, K. Borch-Johnsen, S. S. Rasmussen, et al. (2008)
Diabetes 57, 95-101
   Abstract »    Full Text »    PDF »
Genome-wide selection of tag SNPs using multiple-marker correlation.
K. Hao (2007)
Bioinformatics 23, 3178-3184
   Abstract »    Full Text »    PDF »
A 100K Genome-Wide Association Scan for Diabetes and Related Traits in the Framingham Heart Study: Replication and Integration With Other Genome-Wide Datasets.
J. C. Florez, A. K. Manning, J. Dupuis, J. McAteer, K. Irenze, L. Gianniny, D. B. Mirel, C. S. Fox, L. A. Cupples, and J. B. Meigs (2007)
Diabetes 56, 3063-3074
   Abstract »    Full Text »    PDF »
Genetics of Cardiovascular Diseases: From Single Mutations to the Whole Genome.
F. Cambien and L. Tiret (2007)
Circulation 116, 1714-1724
   Full Text »    PDF »
Review: Genetics of the cardiometabolic syndrome: new insights and therapeutic implications.
S. Sookoian and C. J. Pirola (2007)
Therapeutic Advances in Cardiovascular Disease 1, 37-47
   Abstract »    PDF »
Genetic Susceptibility to Peripheral Arterial Disease: A Dark Corner in Vascular Biology.
J. W. Knowles, T. L. Assimes, J. Li, T. Quertermous, and J. P. Cooke (2007)
Arterioscler Thromb Vasc Biol 27, 2068-2078
   Abstract »    Full Text »    PDF »
Association of variants in the BAT1-NFKBIL1-LTA genomic region with protection against myocardial infarction in Europeans.
W. Koch, P. Hoppmann, E. Michou, V. Jung, A. Pfeufer, J. C. Mueller, C. Gieger, H.-E. Wichmann, T. Meitinger, A. Schomig, et al. (2007)
Hum. Mol. Genet. 16, 1821-1827
   Abstract »    Full Text »    PDF »
Genetic Susceptibility, HIV Infection, and the Kidney.
K. Kiryluk, J. Martino, and A. G. Gharavi (2007)
Clin. J. Am. Soc. Nephrol. 2, S25-S35
   Abstract »    Full Text »    PDF »
Genetic Epidemiology of Obesity.
W. Yang, T. Kelly, and J. He (2007)
Epidemiol. Rev.
   Abstract »    Full Text »    PDF »
Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group.
D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. (2007)
Circulation 115, 2878-2901
   Abstract »    Full Text »    PDF »
Effect of an Estrogen Receptor-{alpha} Intron 4 Polymorphism on Fat Mass in 11-Year-Old Children.
J. H. Tobias, C. D. Steer, C. Vilarino-Guell, and M. A. Brown (2007)
J. Clin. Endocrinol. Metab. 92, 2286-2291
   Abstract »    Full Text »    PDF »
Regulation of Hepatic Insig-2 by the Farnesoid X Receptor.
M. L. Hubbert, Y. Zhang, F. Y. Lee, and P. A. Edwards (2007)
Mol. Endocrinol. 21, 1359-1369
   Abstract »    Full Text »    PDF »
A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity.
T. M. Frayling, N. J. Timpson, M. N. Weedon, E. Zeggini, R. M. Freathy, C. M. Lindgren, J. R. B. Perry, K. S. Elliott, H. Lango, N. W. Rayner, et al. (2007)
Science 316, 889-894
   Abstract »    Full Text »    PDF »
Association Studies of BMI and Type 2 Diabetes in the Neuropeptide Y Pathway: A Possible Role for NPY2R as a Candidate Gene for Type 2 Diabetes in Men.
C. D. Campbell, H. N. Lyon, J. Nemesh, J. A. Drake, T. Tuomi, D. Gaudet, X. Zhu, R. S. Cooper, K. G. Ardlie, L. C. Groop, et al. (2007)
Diabetes 56, 1460-1467
   Abstract »    Full Text »    PDF »
Atherosclerosis: The Path From Genomics to Therapeutics.
D. T. Miller, P. M. Ridker, P. Libby, and D. J. Kwiatkowski (2007)
J. Am. Coll. Cardiol. 49, 1589-1599
   Abstract »    Full Text »    PDF »
On the synthesis and interpretation of consistent but weak gene-disease associations in the era of genome-wide association studies.
M. J Khoury, J. Little, M. Gwinn, and J. P. Ioannidis (2007)
Int. J. Epidemiol. 36, 439-445
   Abstract »    Full Text »    PDF »
Integrative Study Designs--Next Step in the Evolution of Molecular Epidemiology?.
N. E. Caporaso (2007)
Cancer Epidemiol. Biomarkers Prev. 16, 365-366
   Full Text »    PDF »
Interpreting Results of Large-Scale Genetic Association Studies: Separating Gold From Fool's Gold.
J. Dupuis and C. J. O'Donnell (2007)
JAMA 297, 529-531
   Full Text »    PDF »
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity".
C. Dina, D. Meyre, C. Samson, J. Tichet, M. Marre, B. Jouret, M. A. Charles, B. Balkau, and P. Froguel (2007)
Science 315, 187b
   Abstract »    Full Text »    PDF »
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity".
R. J. F. Loos, I. Barroso, S. O'Rahilly, and N. J. Wareham (2007)
Science 315, 187c
   Abstract »    Full Text »    PDF »
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity".
D. Rosskopf, A. Bornhorst, C. Rimmbach, C. Schwahn, A. Kayser, A. Kruger, G. Tessmann, I. Geissler, H. K. Kroemer, and H. Volzke (2007)
Science 315, 187d
   Abstract »    Full Text »    PDF »
Response to Comments on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity".
A. Herbert, N. P. Gerry, M. B. McQueen, I. M. Heid, A. Pfeufer, T. Illig, H.-E. Wichmann, T. Meitinger, D. Hunter, F. B. Hu, et al. (2007)
Science 315, 187e
   Abstract »    Full Text »    PDF »
P2BAT: a massive parallel implementation of PBAT for genome-wide association studies in R.
T. Hoffmann and C. Lange (2006)
Bioinformatics 22, 3103-3105
   Abstract »    Full Text »    PDF »
Epistemological issues in omics and high-dimensional biology: give the people what they want.
T. S. Mehta, S. O. Zakharkin, G. L. Gadbury, and D. B. Allison (2006)
Physiol Genomics 28, 24-32
   Abstract »    Full Text »    PDF »
Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Reverse engineering gene networks to identify key drivers of complex disease phenotypes.
E. E. Schadt and P. Y. Lum (2006)
J. Lipid Res. 47, 2601-2613
   Abstract »    Full Text »    PDF »
Common Variants in the ENPP1 Gene Are Not Reproducibly Associated With Diabetes or Obesity.
H. N. Lyon, J. C. Florez, T. Bersaglieri, R. Saxena, W. Winckler, P. Almgren, U. Lindblad, T. Tuomi, D. Gaudet, X. Zhu, et al. (2006)
Diabetes 55, 3180-3184
   Abstract »    Full Text »    PDF »
Common genetic variants for breast cancer: 32 largely refuted candidates and larger prospects..
J. P. A. Ioannidis (2006)
J Natl Cancer Inst 98, 1350-1353
   Full Text »    PDF »
Genetics of obesity in Hispanic children..
J. S Fisler and C. H Warden (2006)
Am. J. Clinical Nutrition 84, 473-474
   Full Text »    PDF »
Researchers Identify Genes Linked to Type 2 Diabetes.
B. Goldfarb (2006)
DOC News 3, 4
   Full Text »
Endocrinology & Metabolism News June 2006.
(2006)
J. Clin. Endocrinol. Metab. 91, 17a
   Full Text »    PDF »
Minerva.
(2006)
BMJ 332, 1042
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)