Clinical References for
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Science
Journal of the American Association for the Advancement of Science

"A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity."

Timothy M. Frayling, Nicholas J. Timpson, Michael N. Weedon, Eleftheria Zeggini, Rachel M. Freathy, Cecilia M. Lindgren, John R. B. Perry, Katherine S. Elliott, Hana Lango, Nigel W. Rayner, Beverley Shields, Lorna W. Harries, Jeffrey C. Barrett, Sian Ellard, Christopher J. Groves, Bridget Knight, Ann-Marie Patch, Andrew R. Ness, Shah Ebrahim, Debbie A. Lawlor, Susan M. Ring, Yoav Ben-Shlomo, Marjo-Riitta Jarvelin, Ulla Sovio, Amanda J. Bennett, David Melzer, Luigi Ferrucci, Ruth J. F. Loos, Inês Barroso, Nicholas J. Wareham, Fredrik Karpe, Katharine R. Owen, Lon R. Cardon, Mark Walker, Graham A. Hitman, Colin N. A. Palmer, Alex S. F. Doney, Andrew D. Morris, George Davey-Smith, The Wellcome Trust Case Control Consortium, Andrew T. Hattersley, and Mark I. McCarthy.


1
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK; Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, UK.
2
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK; The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Rd, Bristol, UK.
3
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
4
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK.
5
Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, UK.
6
Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, UK; The Molecular Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Old Pathology Building, Barrack Road, Exeter, UK.
7
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
8
Department of Oral & Dental Science, Lower Maudlin Street, Bristol, UK.
9
Department of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK.
10
Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, UK.
11
Department of Epidemiology and Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK; Department of Public Health Science and General Practice, Fin-90014, University of Oulu, Finland.
12
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK; Epidemiology and Public Health Group, Peninsula Medical School, Barrack Road, Exeter, UK.
13
Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
14
MRC Epidemiology Unit, Strangeways Research Laboratories, Cambridge, UK.
15
Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
16
Diabetes Research Group, School of Clinical Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, UK.
17
Centre for Diabetes and Metabolic Medicine, Barts and The London, Royal London Hospital, Whitechapel, London, UK.
18
Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK.
19
Diabetes Research Group, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK.
20
The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Rd, Bristol, UK.
21
Membership of the Wellcome Trust Case Control Consortium is listed in the Supporting Online Material.




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

Using gene expression to investigate the genetic basis of complex disorders.

A. C. Nica and E. T. Dermitzakis (2008)
Hum. Mol. Genet. 17, R129-R134

Practical aspects of imputation-driven meta-analysis of genome-wide association studies.

P. I.W. de Bakker, M. A.R. Ferreira, X. Jia, B. M. Neale, S. Raychaudhuri, and B. F. Voight (2008)
Hum. Mol. Genet. 17, R122-R128

Genome-wide association studies: potential next steps on a genetic journey.

M. I. McCarthy and J. N. Hirschhorn (2008)
Hum. Mol. Genet. 17, R156-R165

Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the Cardiovascular Risk in Young Finns study.

M. Kivimaki, G. D. Smith, N. J. Timpson, D. A. Lawlor, G. D. Batty, M. Kahonen, M. Juonala, T. Ronnemaa, J. S.A. Viikari, T. Lehtimaki, et al. (2008)
Eur. Heart J. 29, 2552-2560

The fat mass-and obesity-associated locus and dietary intake in children.

N. J Timpson, P. M Emmett, T. M Frayling, I. Rogers, A. T Hattersley, M. I McCarthy, and G. Davey Smith (2008)
Am. J. Clinical Nutrition 88, 971-978

Corrigendum.

(2008)
Am J Physiol Regulatory Integrative Comp Physiol 295, R1360-R1363

FTO Variants Are Associated With Obesity in the Chinese and Malay Populations in Singapore.

J. T. Tan, R. Dorajoo, M. Seielstad, X. L. Sim, R. T.-H. Ong, K. S. Chia, T. Y. Wong, S. M. Saw, S. K. Chew, T. Aung, et al. (2008)
Diabetes 57, 2851-2857

Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity.

E. Rampersaud, B. D. Mitchell, T. I. Pollin, M. Fu, H. Shen, J. R. O'Connell, J. L. Ducharme, S. Hines, P. Sack, R. Naglieri, et al. (2008)
Arch Intern Med 168, 1791-1797

Genes, exercise, growth, and the sedentary, obese child.

M. Teran-Garcia, T. Rankinen, and C. Bouchard (2008)
J Appl Physiol 105, 988-1001

Obesity Associated Genetic Variation in FTO Is Associated with Diminished Satiety.

J. Wardle, S. Carnell, C. M. A. Haworth, I. S. Farooqi, S. O'Rahilly, and R. Plomin (2008)
J. Clin. Endocrinol. Metab. 93, 3640-3643

Genomewide Association Analysis Followed by a Replication Study Implicates a Novel Candidate Gene for Neuroticism.

E. J. C. G. van den Oord, P.-H. Kuo, A. M. Hartmann, B. T. Webb, H.-J. Moller, J. M. Hettema, I. Giegling, J. Bukszar, and D. Rujescu (2008)
Arch Gen Psychiatry 65, 1062-1071

Addictions Biology: Haplotype-Based Analysis for 130 Candidate Genes on a Single Array.

C. A. Hodgkinson, Q. Yuan, K. Xu, P.-H. Shen, E. Heinz, E. A. Lobos, E. B. Binder, J. Cubells, C. L. Ehlers, J. Gelernter, et al. (2008)
Alcohol Alcohol. 43, 505-515

Association Testing of Novel Type 2 Diabetes Risk Alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 Loci With Insulin Release, Insulin Sensitivity, and Obesity in a Population-Based Sample of 4,516 Glucose-Tolerant Middle-Aged Danes.

N. Grarup, G. Andersen, N. T. Krarup, A. Albrechtsen, O. Schmitz, T. Jorgensen, K. Borch-Johnsen, T. Hansen, and O. Pedersen (2008)
Diabetes 57, 2534-2540

Replication of Genome-Wide Association Studies of Type 2 Diabetes Susceptibility in Japan.

Y. Horikawa, K. Miyake, K. Yasuda, M. Enya, Y. Hirota, K. Yamagata, Y. Hinokio, Y. Oka, N. Iwasaki, Y. Iwamoto, et al. (2008)
J. Clin. Endocrinol. Metab. 93, 3136-3141

Association Analysis in African Americans of European-Derived Type 2 Diabetes Single Nucleotide Polymorphisms From Whole-Genome Association Studies.

J. P. Lewis, N. D. Palmer, P. J. Hicks, M. M. Sale, C. D. Langefeld, B. I. Freedman, J. Divers, and D. W. Bowden (2008)
Diabetes 57, 2220-2225

Implication of Genetic Variants Near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in Type 2 Diabetes and Obesity in 6,719 Asians.

M. C.Y. Ng, K. S. Park, B. Oh, C. H.T. Tam, Y. M. Cho, H. D. Shin, V. K.L. Lam, R. C.W. Ma, W. Y. So, Y. S. Cho, et al. (2008)
Diabetes 57, 2226-2233

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

Genomics in cardiac metabolism.

J.-L. Samuel, M. C. Schaub, M. Zaugg, M. Mamas, W. B. Dunn, and B. Swynghedauw (2008)
Cardiovasc Res 79, 218-227

Appetite and adiposity in children: evidence for a behavioral susceptibility theory of obesity.

S. Carnell and J. Wardle (2008)
Am. J. Clinical Nutrition 88, 22-29

Development of a single tube 640-plex genotyping method for detection of nucleic acid variations on microarrays.

K. Krjutskov, R. Andreson, R. Magi, T. Nikopensius, A. Khrunin, E. Mihailov, V. Tammekivi, H. Sork, M. Remm, and A. Metspalu (2008)
Nucleic Acids Res. 36, e75

Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation.

J. H. White, M. Chiano, M. Wigglesworth, R. Geske, J. Riley, N. White, S. Hall, G. Zhu, F. Maurio, T. Savage, et al. (2008)
Hum. Mol. Genet. 17, 1890-1903

Lack of Association of Fatness-Related FTO Gene Variants with Energy Expenditure or Physical Activity.

T. Berentzen, S. I. I. Kring, C. Holst, E. Zimmermann, T. Jess, T. Hansen, O. Pedersen, S. Toubro, A. Astrup, and T. I. A. Sorensen (2008)
J. Clin. Endocrinol. Metab. 93, 2904-2908

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

Microarray Technology and Applications in the Arena of Genome-Wide Association.

S. F. A. Grant and H. Hakonarson (2008)
Clin. Chem. 54, 1116-1124

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

Reporting and interpretation in genome-wide association studies.

J. Wakefield (2008)
Int. J. Epidemiol. 37, 641-653

The Obesity Gene, FTO, Is of Ancient Origin, Up-Regulated during Food Deprivation and Expressed in Neurons of Feeding-Related Nuclei of the Brain.

R. Fredriksson, M. Hagglund, P. K. Olszewski, O. Stephansson, J. A. Jacobsson, A. M. Olszewska, A. S. Levine, J. Lindblom, and H. B. Schioth (2008)
Endocrinology 149, 2062-2071

Recent advances in the molecular pathology, cell biology and genetics of ciliopathies.

M Adams, U M Smith, C V Logan, and C A Johnson (2008)
J. Med. Genet. 45, 257-267

Common Variation in the FTO Gene Alters Diabetes-Related Metabolic Traits to the Extent Expected Given Its Effect on BMI.

R. M. Freathy, N. J. Timpson, D. A. Lawlor, A. Pouta, Y. Ben-Shlomo, A. Ruokonen, S. Ebrahim, B. Shields, E. Zeggini, M. N. Weedon, et al. (2008)
Diabetes 57, 1419-1426

A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function.

J. M. C. Connell, S. M. MacKenzie, E. M. Freel, R. Fraser, and E. Davies (2008)
Endocr. Rev. 29, 133-154

The Association between the FTO Gene and Fat Mass in Humans Develops by the Postnatal Age of Two Weeks.

A. Lopez-Bermejo, C. J. Petry, M. Diaz, G. Sebastiani, F. de Zegher, D. B. Dunger, and L. Ibanez (2008)
J. Clin. Endocrinol. Metab. 93, 1501-1505

Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study.

R. Do, S. D. Bailey, K. Desbiens, A. Belisle, A. Montpetit, C. Bouchard, L. Perusse, M.-C. Vohl, and J. C. Engert (2008)
Diabetes 57, 1147-1150

How to Interpret a Genome-wide Association Study.

T. A. Pearson and T. A. Manolio (2008)
JAMA 299, 1335-1344

The FTO (fat mass and obesity-associated) gene: big in adipocyte lipolysis?.

C. C. Shoulders (2008)
J. Lipid Res. 49, 495-496

The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis.

K. Wahlen, E. Sjolin, and J. Hoffstedt (2008)
J. Lipid Res. 49, 607-611

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

Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 With Susceptibility to Type 2 Diabetes in a Japanese Population.

S. Omori, Y. Tanaka, A. Takahashi, H. Hirose, A. Kashiwagi, K. Kaku, R. Kawamori, Y. Nakamura, and S. Maeda (2008)
Diabetes 57, 791-795

A Candidate Type 2 Diabetes Polymorphism Near the HHEX Locus Affects Acute Glucose-Stimulated Insulin Release in European Populations: Results from the EUGENE2 study.

H. Staiger, A. Stancakova, J. Zilinskaite, M. Vanttinen, T. Hansen, M. A. Marini, A. Hammarstedt, P.-A. Jansson, G. Sesti, U. Smith, et al. (2008)
Diabetes 57, 514-517

Required sample size and nonreplicability thresholds for heterogeneous genetic associations.

R. Moonesinghe, M. J. Khoury, T. Liu, and J. P. A. Ioannidis (2008)
PNAS 105, 617-622

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 »

Variants in the Fat Mass and Obesity-Associated (FTO) Gene Are Not Associated With Obesity in a Chinese Han Population.

H. Li, Y. Wu, R. J.F. Loos, F. B. Hu, Y. Liu, J. Wang, Z. Yu, and X. Lin (2008)
Diabetes 57, 264-268

Origins of magic: review of genetic and epigenetic effects.

S. V Ramagopalan, M. Knight, G. C Ebers, and J. C Knight (2007)
BMJ 335, 1299-1301

Common Variants of the Novel Type 2 Diabetes Genes CDKAL1 and HHEX/IDE Are Associated With Decreased Pancreatic {beta}-Cell Function.

L. Pascoe, A. Tura, S. K. Patel, I. M. Ibrahim, E. Ferrannini, E. Zeggini, M. N. Weedon, A. Mari, A. T. Hattersley, M. I. McCarthy, et al. (2007)
Diabetes 56, 3101-3104

Evolving a definition of disease.

P. D Gluckman (2007)
Arch. Dis. Child. 92, 1053-1054

The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase.

T. Gerken, C. A. Girard, Y.-C. L. Tung, C. J. Webby, V. Saudek, K. S. Hewitson, G. S. H. Yeo, M. A. McDonough, S. Cunliffe, L. A. McNeill, et al. (2007)
Science 318, 1469-1472

Future Use of Genomics in Coronary Artery Disease.

S. B. Damani and E. J. Topol (2007)
J. Am. Coll. Cardiol. 50, 1933-1940

Genetics of Cardiovascular Diseases: From Single Mutations to the Whole Genome.

F. Cambien and L. Tiret (2007)
Circulation 116, 1714-1724

NO to Obesity: Does Nitric Oxide Regulate Fat Oxidation and Insulin Sensitivity?.

H.-G. Joost and M. H. Tschop (2007)
Endocrinology 148, 4545-4547

Muscling in on the genetics of quantitative disease traits.

P. W. Franks (2007)
J Appl Physiol 103, 1111-1112

ATP-sensitive K+ channels and disease: from molecule to malady.

F. M. Ashcroft (2007)
Am J Physiol Endocrinol Metab 293, E880-E889

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

Assessing the social meaning, value and implications of research in genomics.

B. Lumbreras, M. Porta, and I. Hernandez-Aguado (2007)
J. Epidemiol. Community Health 61, 755-756

Tyrosine Hydroxylase: Another Piece of the Genetics of Hypertension Puzzle.

S. C. Hunt (2007)
Circulation 116, 970-972

Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene.

F. Stutzmann, V. Vatin, S. Cauchi, A. Morandi, B. Jouret, O. Landt, P. Tounian, C. Levy-Marchal, R. Buzzetti, L. Pinelli, et al. (2007)
Hum. Mol. Genet. 16, 1837-1844

Network Medicine -- From Obesity to the "Diseasome".

A.-L. Barabasi (2007)
N. Engl. J. Med. 357, 404-407

The Genomics Gold Rush.

E. J. Topol, S. S. Murray, and K. A. Frazer (2007)
JAMA 298, 218-221

Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes.

E. Zeggini, M. N. Weedon, C. M. Lindgren, T. M. Frayling, K. S. Elliott, H. Lango, N. J. Timpson, J. R. B. Perry, N. W. Rayner, R. M. Freathy, et al. (2007)
Science 316, 1336-1341

A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants.

L. J. Scott, K. L. Mohlke, L. L. Bonnycastle, C. J. Willer, Y. Li, W. L. Duren, M. R. Erdos, H. M. Stringham, P. S. Chines, A. U. Jackson, et al. (2007)
Science 316, 1341-1345







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