A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity
Open accessAbstract
Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetesâsusceptibility genes identified a common variant in the FTO (fat mass and obesity associated) gene that predisposes to diabetes through an effect on body mass index (BMI). An additive association of the variant with BMI was replicated in 13 cohorts with 38,759 participants. The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The FTO gene influences hypothalamic regulation of appetite and energy expenditure by modulating leptin and melanocortin signaling pathways.
“Key genes, such as the fat mass and obesity-associated gene (FTO), influence hypothalamic regulation of appetite and energy expenditure by modulating leptin and melanocortin signaling pathways [22].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [22]
The paper reports that FTO variation is associated with BMI and obesity, and that FTO expression is highest in the brain (passages indexed under Abstract; page unavailable). It does not establish hypothalamic regulation of appetite or energy expenditure through leptin and melanocortin signaling. Instead, it describes FTO as having an unknown function in an unknown pathway and calls for further work to identify the mechanism. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe 16% of sedentary adults homozygous for the risk allele AA in rs9939609 in the FTO gene weighed about 3 kg more and had 1.67-fold increased odds of obesity compared with those not inheriting a risk allele.
“The 16% of sedentary adults who are homozygous for the risk allele of AA in rs9939609 in the fat mass and obesity-associated (FTO) gene weighed ~3 kg more and had 1.67-fold increased odds of obesity when compared with those not inheriting a risk allele (191).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [191]
Similar results were also obtained using a genetic risk score based solely on the SNP in the FTO gene.
“Secondly, similar results were also obtained using a genetic risk score based solely on the SNP in the FTO gene, which is a gene that has been found to be associated with BMI in numerous studies, where none of the cohorts used in the present study were included [34–36].”
From Causal relationship between obesity and serum testosterone status in men: A bi-directional mendelian randomization analysis (2017) · cites this paper as [34]
Variants at the four BMI loci have also been associated with childhood BMI.
“Variants at these four loci have also been associated with childhood BMI18–20”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [18]
Four novel loci for menarche were previously identified by GWA studies for adult BMI: rs9939609 (in/near FTO, P=3.1×10−8), rs633715 (SEC16B, P=2.1×10−8), rs2002675 (TRA2B, ETV5, P=1.2×10−9) and rs2947411 (TMEM18, P=1.7×10−8).
“Four novel loci for menarche were previously identified by GWA studies for adult BMI18–20; these were rs9939609 (in/near FTO, P=3.1×10−8), rs633715 (SEC16B, P=2.1×10−8), rs2002675 (TRA2B, ETV5, P=1.2×10−9) and rs2947411 (TMEM18, P=1.7×10−8).”
From Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies (2010) · cites this paper as [18]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · see citing works
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248 · see citing works
Prevalence of Overweight and Obesity in the United States, 1999-2004
Ogden, C. L., Carroll, M. D., Curtin, L. R., McDowell, M. A., Tabak, C. J., & Flegal, K. M. (2006) · JAMA · doi:10.1001/jama.295.13.1549 · Cited by 8,720 · see citing works
Obesity in children and young people: a crisis in public health
Lobstein, T., Baur, L., & Uauy, R. (2004) · Obesity Reviews · doi:10.1111/j.1467-789x.2004.00133.x · Cited by 3,801 · see citing works
Genetic and Environmental Factors in Relative Body Weight and Human Adiposity
Maes, H. H. M., Neale, M. C., & Eaves, L. J. (1997) · Behavior Genetics · doi:10.1023/a:1025635913927 · Cited by 1,515 · see citing works
A common genetic variant is associated with adult and childhood obesity.
Herbert, A., Gerry, N. P., McQueen, M. B., Heid, I. M., Pfeufer, A., Illig, T., Wichmann, H.-E., Meitinger, T., Hunter, D., Hu, F. B., et al. (2006) · Science · doi:10.1126/science.1124779 · Cited by 732 · see citing works
Farooqi, I. S., & O’Rahilly, S. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0040 · Cited by 583 · see citing works
Meyre, D., Bouatia‐Naji, N., Tounian, A., Samson, C., Lecœur, C., Vatin, V., Ghoussaini, M., Wachter, C., Herçberg, S., Charpentier, G., et al. (2005) · Nature Genetics · doi:10.1038/ng1604 · Cited by 316 · see citing works
GAD2 on Chromosome 10p12 Is a Candidate Gene for Human Obesity
Boutin, P., Christian Dina, C., Vasseur, F., Dubois, S. G., Corset, L., Séron, K., Bekris, L. M., Cabellon, J., NEVE, B. P., Vasseur-Delannoy, V., et al. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000068 · Cited by 149 · see citing works
Programmed cell death is affected in the novel mouse mutant Fused toes (Ft)
van der Hoeven, F., Schimmang, T., Volkmann, A., Mattéi, M., Kyewski, B., & Rüther, U. (1994) · Development · doi:10.1242/dev.120.9.2601 · Cited by 141 · see citing works
Zhang, S., Zhu, X., & Zhao, H. (2002) · Genetic Epidemiology · doi:10.1002/gepi.10196 · Cited by 98 · see citing works
Peters, T., Ausmeier, K., Dildrop, R., et al. (2002) · Mammalian Genome · doi:10.1007/s00335-001-2142-7 · Cited by 90 · see citing works
Weedon, M. N., Shields, B. M., Hitman, G. A., Walker, M., McCarthy, M. I., Hattersley, A. T., & Frayling, T. M. (2006) · Diabetes · doi:10.2337/db06-0410 · Cited by 88 · see citing works
Self-citationGroves, C. J., Zeggini, E., Walker, M., Hitman, G. A., Lévy, J., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., & Wiltshire, S. (2006) · Diabetes · doi:10.2337/db05-1674 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 17
- [1]1. Ogden CL, et al. JAMA 2006;295:1549. [PubMed: 16595758]
- [2]2. Maes HHM, Neale MC, Eaves LJ. Behav Genet 1997;27:325. [PubMed: 9519560]
- [4]4. Boutin P, et al. PLoS Biol 2003;1:361.
- [5]5. Meyre D, et al. Nat Genet 2005;37:863. [PubMed: 16025115]
- [6]6. Swarbrick MM, et al. PLoS Biol 2005;3:1662.
- [7]7. Groves CJ, et al. Diabetes 2006;55:1884. [PubMed: 16731858]
- [8]8. Weedon MN, et al. Diabetes 2006;55:3175. [PubMed: 17065358]
- [9]9. Herbert A, et al. Science 2006;312:279. [PubMed: 16614226]
- [10]10. Loos RJF, Barroso I, O'Rahilly S, Wareham NJ. Science 2007;315:179c.
- [11]11. Rosskopf D, et al. Science 2007;315:179d.
- [12]12. Dina C, et al. Science 2007;315:179b.
- [14]14. Higgins JP, Thompson SG, Deeks JJ, Altman DG. BMJ 2003;327:557. [PubMed: 12958120]
- [15]15. Lobstein T, Baur L, Uauy R. Obes Rev 2004;5:4. [PubMed: 15096099]
- [16]16. Zhang S, Zhu X, Zhao H. Genet Epidemiol 2003;24:44. [PubMed: 12508255]
- [17]17. Price AL, et al. Nat Genet 2006;38:904. [PubMed: 16862161]
- [18]18. Peters T, Ausmeier K, Dildrop R, Rüther U. Mamm Genome 2002;13:186. [PubMed: 11956760]
- [19]19. van der Hoeven F, et al. Development 1994;120:2601. [PubMed: 7956835]
Cited by
Sorted by citations
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
Self-citationHeart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association
Virani, S. S., Alonso, A., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Delling, F. N., et al. (2020) · Circulation · doi:10.1161/cir.0000000000000757 · Cited by 9,175 · see citing works
Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association
Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Das, S. R., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000659 · Cited by 9,036 · see citing works
Heart disease and stroke statistics-2018 update: a report from the american heart association
Benjamin, E. J., Virani, S. S., Callaway, C. W., Chamberlain, A. M., Chang, A. R., Cheng, S., Chiuve, S. E., Cushman, M., Delling, F. N., Deo, R., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000558 · Cited by 7,146 · see citing works
Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001052 · Cited by 5,987 · see citing works
Obesity: global epidemiology and pathogenesis
Blüher, M. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0176-8 · Cited by 5,126 · see citing works
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
Davey Smith, G., & Hemani, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu328 · Cited by 4,677 · see citing works
Richness of human gut microbiome correlates with metabolic markers
Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-M., Kennedy, S., et al. (2013) · Nature · doi:10.1038/nature12506 · Cited by 4,662 · see citing works
N6-methyladenosine-dependent regulation of messenger RNA stability
Wang, X., Lu, Z., Gomez, A., Hon, G. C., Yue, Y., Han, D., Fu, Y., Parisien, M., Dai, Q., Jia, G., et al. (2014) · Nature · doi:10.1038/nature12730 · Cited by 4,558 · see citing works
N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.-G., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.687 · Cited by 4,106 · see citing works
ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
Zheng, G., Dahl, J. A., Niu, Y., Fedorcsak, P., Huang, C.-M., Li, C. J., Vågbø, C. B., Shi, Y., Wang, W.-L., Song, S.-H., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.015 · Cited by 3,550 · see citing works
Human Genetics Shape the Gut Microbiome
Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J. T., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.053 · Cited by 3,164 · see citing works
Boyd, A., Golding, J., Macleod, J., Lawlor, D. A., Fraser, A., Henderson, J., Molloy, L., Ness, A., Ring, S., & Davey Smith, G. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dys064 · Cited by 2,996 · see citing works
Self-citationAssociation analyses of 249,796 individuals reveal 18 new loci associated with body mass index
MAGIC, Speliotes, E. K., on behalf of Procardis Consortium, Willer, C. J., Berndt, S. I., Monda, K. L., Thorleifsson, G., Jackson, A. U., Allen, H. L., Lindgren, C. M., et al. (2010) · Nature Genetics · doi:10.1038/ng.686 · Cited by 2,912 · see citing works
Self-citationGenome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., & Hirschhorn, J. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2344 · Cited by 2,891 · see citing works
Self-citationA genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U., et al. (2007) · Science · doi:10.1126/science.1142382 · Cited by 2,753 · see citing works
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Cohort Profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort
Fraser, A., Macdonald-Wallis, C., Tilling, K., Boyd, A., Golding, J., Davey Smith, G., Henderson, J., Macleod, J., Molloy, L., Ness, A., et al. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dys066 · Cited by 2,494 · see citing works
Self-citationVisscher, P. M., Brown, M. A., McCarthy, M. I., & Yang, J. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.029 · Cited by 2,425 · see citing works
Self-citationThe role of m6A modification in the biological functions and diseases
Jiang, X., Liu, B., Nie, Z., Duan, L., Xiong, Q., Jin, Z., Yang, C., & Chen, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00450-x · Cited by 2,335 · see citing works
Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes
Zeggini, E., Weedon, M. N., Lindgren, C. M., Frayling, T. M., Elliott, K. S., Lango, H., Timpson, N. J., Perry, J. R. B., Rayner, N. W., Freathy, R. M., et al. (2007) · Science · doi:10.1126/science.1142364 · Cited by 2,194 · see citing works
Self-citationDiamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947 · see citing works
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967 · see citing works
Garvey, W. T., Mechanick, J. I., Brett, E. M., Garber, A. J., Hurley, D. L., Jastreboff, A. M., Nadolsky, K., Pessah-Pollack, R., & Plodkowski, R. (2016) · Endocrine Practice · doi:10.4158/ep161365.gl · Cited by 1,914 · see citing works
Genome-wide association studies
Uffelmann, E., Huang, Q. Q., Munung, N. S., de Vries, J., Okada, Y., Martin, A. R., Martin, H. C., Lappalainen, T., & Posthuma, D. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00056-9 · Cited by 1,849 · see citing works
Scuteri, A., Sanna, S., Chen, W.-M., Uda, M., Albai, G., Strait, J., Najjar, S., Nagaraja, R., Orrú, M., Usala, G., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030115 · Cited by 1,724 · see citing works
the GIANT Consortium (2009) · Nature Genetics · doi:10.1038/ng.287 · Cited by 1,720 · see citing works
<i>FTO</i> Obesity Variant Circuitry and Adipocyte Browning in Humans
Claussnitzer, M., Dankel, S. N., Kim, K.-H., Quon, G., Meuleman, W., Haugen, C., Glunk, V., Sousa, I. S., Beaudry, J. L., Puviindran, V., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1502214 · Cited by 1,332 · see citing works
Detecting gene–gene interactions that underlie human diseases
Cordell, H. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2579 · Cited by 1,350 · see citing works
Thorleifsson, G., Walters, G. B., Gudbjartsson, D. F., Steinthorsdottir, V., Sulem, P., Helgadottir, A., Styrkarsdottir, U., Gretarsdottir, S., Thorlacius, S., Jonsdottir, I., et al. (2009) · Nature Genetics · doi:10.1038/ng.274 · Cited by 1,375 · see citing works
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09101452 · Cited by 1,346 · see citing works
The genetics of obesity: From discovery to biology
Loos, R. J. F., & Yeo, G. S. H. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00414-z · Cited by 1,291 · see citing works
Self-citationCommon variants near MC4R are associated with fat mass, weight and risk of obesity
The Prostate, L., Loos, R. J. F., KORA, Study, N. H., Initiative, D. G., Study, T. S., The Wellcome Trust Case Control Consortium, FUSION, Lindgren, C. M., Li, S., et al. (2008) · Nature Genetics · doi:10.1038/ng.140 · Cited by 1,325 · see citing works
Self-citationObesity-associated variants within FTO form long-range functional connections with IRX3
Smemo, S., Tena, J. J., Kim, K.-H., Gamazon, E. R., Sakabe, N. J., Gómez-Marín, C., Aneas, I., Credidio, F. L., Sobreira, D. R., Wasserman, N. F., et al. (2014) · Nature · doi:10.1038/nature13138 · Cited by 1,219 · see citing works
Using multiple genetic variants as instrumental variables for modifiable risk factors
Palmer, T. M., Lawlor, D. A., Harbord, R. M., Sheehan, N. A., Tobias, J. H., Timpson, N. J., Smith, G. D., & Sterne, J. A. (2012) · Statistical Methods in Medical Research · doi:10.1177/0962280210394459 · Cited by 1,289 · see citing works
The microbiome in early life: Implications for health outcomes
Tamburini, S., Shen, N., Wu, H. C., & Clemente, J. C. (2016) · Nature Medicine · doi:10.1038/nm.4142 · Cited by 1,213 · see citing works
Uncovering the roles of rare variants in common disease through whole-genome sequencing
Cirulli, E. T., & Goldstein, D. B. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2779 · Cited by 1,136 · see citing works
Human genetic variation and its contribution to complex traits
Frazer, K. A., Murray, S. S., Schork, N. J., & Topol, E. J. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2554 · Cited by 1,073 · see citing works
Identification of loci associated with schizophrenia by genome-wide association and follow-up
Molecular Genetics of Schizophrenia Collaboration, O'Donovan, M. C., Craddock, N., Norton, N., Williams, H., Peirce, T., Moskvina, V., Nikolov, I., Hamshere, M., Carroll, L., et al. (2008) · Nature Genetics · doi:10.1038/ng.201 · Cited by 1,070 · see citing works
Zhang, C., Zhang, M., Wang, S., Han, R., Cao, Y., Hua, W., Mao, Y., Zhang, X., Pang, X., Wei, C., et al. (2010) · The ISME Journal · doi:10.1038/ismej.2009.112 · Cited by 1,024 · see citing works
The role of regulatory variation in complex traits and disease
Albert, F. W., & Kruglyak, L. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3891 · Cited by 1,047 · see citing works
Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J., Batterham, R. L., Benoit, S. C., Bowers, C. Y., Broglio, F., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.005 · Cited by 1,034 · see citing works
Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome
Maury, E., & Brichard, S. M. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.07.031 · Cited by 1,026 · see citing works
Anti-obesity drug discovery: advances and challenges
Müller, T. D., Blüher, M., Tschöp, M. H., & DiMarchi, R. D. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00337-8 · Cited by 1,021 · see citing works
Clinical risk factors, DNA variants, and the development of type 2 diabetes
Lyssenko, V., Jonsson, A., Almgren, P., Pulizzi, N., Isomaa, B., Tuomi, T., Berglund, G., Altshuler, D., Nilsson, P., & Groop, L. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0801869 · Cited by 938 · see citing works
Genomics, type 2 diabetes, and obesity
McCarthy, M. I. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0906948 · Cited by 938 · see citing works
Self-citationMAGIC, Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, E. K., et al. (2010) · Nature Genetics · doi:10.1038/ng.685 · Cited by 931 · see citing works
Self-citationVariations in DNA elucidate molecular networks that cause disease
Chen, Y., Zhu, J., Lum, P. Y., Yang, X., Pinto, S., MacNeil, D. J., Zhang, C., Lamb, J., Edwards, S., Sieberts, S. K., et al. (2008) · Nature · doi:10.1038/nature06757 · Cited by 887 · see citing works
A HapMap harvest of insights into the genetics of common disease
Manolio, T. A., Brooks, L. D., & Collins, F. S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34772 · Cited by 889 · see citing works
Genome partitioning of genetic variation for complex traits using common SNPs
Yang, J., Manolio, T. A., Pasquale, L. R., Boerwinkle, E., Caporaso, N., Cunningham, J. M., de Andrade, M., Feenstra, B., Feingold, E., Hayes, M. G., et al. (2011) · Nature Genetics · doi:10.1038/ng.823 · Cited by 890 · see citing works
Rare independent mutations in renal salt handling genes contribute to blood pressure variation
Ji, W., Foo, J. N., O'Roak, B. J., Zhao, H., Larson, M. G., Simon, D. B., Newton-Cheh, C., State, M. W., Levy, D., & Lifton, R. P. (2008) · Nature Genetics · doi:10.1038/ng.118 · Cited by 812 · see citing works
The Genetics of Major Depression
Flint, J., & Kendler, K. S. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.027 · Cited by 724 · see citing works
Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms
Booth, F. W., Roberts, C. K., Thyfault, J. P., Ruegsegger, G. N., & Toedebusch, R. G. (2017) · Physiological Reviews · doi:10.1152/physrev.00019.2016 · Cited by 696 · see citing works
Common disorders are quantitative traits
Plomin, R., Haworth, C. M. A., & Davis, O. S. P. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2670 · Cited by 670 · see citing works
Large, rare chromosomal deletions associated with severe early-onset obesity
Bochukova, E. G., Huang, N., Keogh, J., Henning, E., Purmann, C., Blaszczyk, K., Saeed, S., Hamilton-Shield, J., Clayton-Smith, J., O’Rahilly, S., et al. (2010) · Nature · doi:10.1038/nature08689 · Cited by 613 · see citing works
Practical aspects of imputation-driven meta-analysis of genome-wide association studies
de Bakker, P. I. W., Ferreira, M. A. R., Jia, X., Neale, B. M., Raychaudhuri, S., & Voight, B. F. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn288 · Cited by 531 · see citing works
A clinical perspective of obesity, metabolic syndrome and cardiovascular disease
Han, T. S., & Lean, M. E. (2016) · JRSM Cardiovascular Disease · doi:10.1177/2048004016633371 · Cited by 500 · see citing works
Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
Mehran, A. E., Templeman, N. M., Brigidi, G. S., Lim, G. E., Chu, K.-Y., Hu, X., Botezelli, J. D., Asadi, A., Hoffman, B. G., Kieffer, T. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.019 · Cited by 498 · see citing works
Nguyen, D. M., & El-Serag, H. B. (2010) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2009.12.014 · Cited by 531 · see citing works
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
The GIANT Consortium, Elks, C. E., Perry, J. R. B., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., et al. (2010) · Nature Genetics · doi:10.1038/ng.714 · Cited by 504 · see citing works
Self-citationA genome-wide association study identifies protein quantitative trait loci (pQTLs)
Melzer, D., Perry, J. R. B., Hernandez, D., Corsi, A.-M., Stevens, K., Rafferty, I., Lauretani, F., Murray, A., Gibbs, J. R., Paolisso, G., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000072 · Cited by 480 · see citing works
Self-citationDrug development in the era of precision medicine
Dugger, S. A., Platt, A., & Goldstein, D. B. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.226 · Cited by 493 · see citing works
Andreasen, C. H., Stender-Petersen, K. L., Mogensen, M. S., Torekov, S. S., Wegner, L., Andersen, G., Nielsen, A. L., Albrechtsen, A., Borch-Johnsen, K., Rasmussen, S. S., et al. (2008) · Diabetes · doi:10.2337/db07-0910 · Cited by 476 · see citing works
Genetics of Type 2 Diabetes—Pitfalls and Possibilities
Prasad, R., & Groop, L. (2015) · Genes · doi:10.3390/genes6010087 · Cited by 458 · see citing works
Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders
Psychiatric GWAS Consortium Coordinating Committee (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08091354 · Cited by 450 · see citing works
The Genetics of Transcription Factor DNA Binding Variation
Deplancke, B., Alpern, D., & Gardeux, V. (2016) · Cell · doi:10.1016/j.cell.2016.07.012 · Cited by 390 · see citing works
Celis-Morales, C., Livingstone, K. M., Marsaux, C. F. M., Macready, A. L., Fallaize, R., O’Donovan, C. B., Woolhead, C., Forster, H., Walsh, M. C., Navas-Carretero, S., et al. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw186 · Cited by 399 · see citing works
Obesity and polycystic ovary syndrome
Barber, T. M., & Franks, S. (2021) · Clinical Endocrinology · doi:10.1111/cen.14421 · Cited by 385 · see citing works
Selecting instruments for Mendelian randomization in the wake of genome-wide association studies.
Swerdlow, D. I., Kuchenbaecker, K. B., Shah, S., Sofat, R., Holmes, M. V., White, J., Mindell, J. S., Kivimaki, M., Brunner, E. J., Whittaker, J. C., et al. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw088 · Cited by 387 · see citing works
Ng, M. C. Y., Park, K. S., Oh, B., Tam, C. H. T., Cho, Y. M., Shin, H. D., Lam, V. K. L., Ma, R. C. W., So, W. Y., Cho, Y. S., et al. (2008) · Diabetes · doi:10.2337/db07-1583 · Cited by 362 · see citing works
Genetics and epigenetics in obesity
Rohde, K., Keller, M., la Cour Poulsen, L., Blüher, M., Kovacs, P., & Böttcher, Y. (2019) · Metabolism · doi:10.1016/j.metabol.2018.10.007 · Cited by 355 · see citing works
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
Kilpeläinen, T. O., Zillikens, M. C., Stančákova, A., Finucane, F. M., Ried, J. S., Langenberg, C., Zhang, W., Beckmann, J. S., Luan, J., Vandenput, L., et al. (2011) · Nature Genetics · doi:10.1038/ng.866 · Cited by 335 · see citing works
Self-citationPhysical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity
Rampersaud, E., Mitchell, B. D., Pollin, T. I., Fu, M., Shen, H., O’Connell, J. R., Ducharme, J. L., Hines, S., Sack, P., Naglieri, R., et al. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.16.1791 · Cited by 299 · see citing works
Whole-genome association study identifies <i>STK39</i> as a hypertension susceptibility gene
Wang, Y., O'Connell, J. R., McArdle, P. F., Wade, J. B., Dorff, S. E., Shah, S. J., Shi, X., Pan, L., Rampersaud, E., Shen, H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808358106 · Cited by 298 · see citing works
Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks
Yang, X., Deignan, J. L., Qi, H., Zhu, J., Qian, S., Zhong, J., Torosyan, G., Majid, S., Falkard, B., Kleinhanz, R. R., et al. (2009) · Nature Genetics · doi:10.1038/ng.325 · Cited by 288 · see citing works
Glymour, M. M., Tchetgen Tchetgen, E. J., & Robins, J. M. (2012) · American Journal of Epidemiology · doi:10.1093/aje/kwr323 · Cited by 292 · see citing works
Akbari, P., Gilani, A., Sosina, O., Kosmicki, J. A., Khrimian, L., Fang, Y.-Y., Persaud, T., Garcia, V., Sun, D., Li, A., et al. (2021) · Science · doi:10.1126/science.abf8683 · Cited by 276 · see citing works
Structural studies on human 2-oxoglutarate dependent oxygenases
McDonough, M. A., Loenarz, C., Chowdhury, R., Clifton, I. J., & Schofield, C. J. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.08.006 · Cited by 280 · see citing works
Loenarz, C., & Schofield, C. J. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.002 · Cited by 274 · see citing works
Adult-onset autoimmune diabetes: current knowledge and implications for management
Buzzetti, R., Zampetti, S., & Maddaloni, E. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.99 · Cited by 271 · see citing works
Ronn, T., Volkov, P., Gillberg, L., Kokosar, M., Perfilyev, A., Jacobsen, A. L., Jorgensen, S. W., Brons, C., Jansson, P.-A., Eriksson, K.-F., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv124 · Cited by 270 · see citing works
What is a representative brain? Neuroscience meets population science
Falk, E. B., Hyde, L. W., Mitchell, C., Faul, J., Gonzalez, R., Heitzeg, M. M., Keating, D. P., Langa, K. M., Martz, M. E., Maslowsky, J., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310134110 · Cited by 265 · see citing works
Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms
Corbin, K. D., Driscoll, K. A., Pratley, R. E., Smith, S. R., Maahs, D. M., Mayer-Davis, E. J., & Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) (2018) · Endocrine Reviews · doi:10.1210/er.2017-00191 · Cited by 262 · see citing works
Smith, G. D. (2008) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2007.00191.x · Cited by 257 · see citing works
Self-citationImpaired insulin action in the human brain: causes and metabolic consequences
Heni, M., Kullmann, S., Preissl, H., Fritsche, A., & Häring, H.-U. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.173 · Cited by 245 · see citing works
Beijers, L., Wardenaar, K. J., van Loo, H. M., & Schoevers, R. A. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0385-5 · Cited by 240 · see citing works
RNA m6A modification and its function in diseases
Tong, J., Flavell, R. A., & Li, H.-B. (2018) · Frontiers of Medicine · doi:10.1007/s11684-018-0654-8 · Cited by 233 · see citing works
Tanaka, T., Ngwa, J. S., van Rooij, F. J., Zillikens, M. C., Wojczynski, M. K., Frazier-Wood, A. C., Houston, D. K., Kanoni, S., Lemaitre, R. N., Luan, J., et al. (2013) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.052183 · Cited by 226 · see citing works
Self-citationGenome-wide association study identifies sequence variants on 6q21 associated with age at menarche
Sulem, P., Gudbjartsson, D. F., Rafnar, T., Holm, H., Olafsdottir, E. J., Olafsdottir, G. H., Jonsson, T., Alexandersen, P., Feenstra, B., Boyd, H. A., et al. (2009) · Nature Genetics · doi:10.1038/ng.383 · Cited by 219 · see citing works
The genetic and epigenetic basis of type 2 diabetes and obesity
Drong, A. W., Lindgren, C. M., & McCarthy, M. I. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.149 · Cited by 212 · see citing works
Self-citationRagvin, A., Moro, E., Fredman, D., Navratilova, P., Drivenes, Ø., Engström, P. G., Alonso, M. E., Mustienes, E. D. L. C., Skarmeta, J. L. G., Tavares, M. J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911591107 · Cited by 211 · see citing works
FTO gene polymorphisms and obesity risk: a meta-analysis
Peng, S., Zhu, Y., Xu, F., Ren, X., Li, X., & Lai, M. (2011) · BMC Medicine · doi:10.1186/1741-7015-9-71 · Cited by 210 · see citing works
O'Rahilly, S., & Farooqi, I. S. (2008) · Diabetes · doi:10.2337/db08-0210 · Cited by 205 · see citing works
Vitamin C in stem cell reprogramming and cancer
Cimmino, L., Neel, B. G., & Aifantis, I. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.04.001 · Cited by 197 · see citing works
The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis
Fall, T., Hägg, S., Mägi, R., Ploner, A., Fischer, K., Horikoshi, M., Sarin, A.-P., Thorleifsson, G., Ladenvall, C., Kals, M., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001474 · Cited by 203 · see citing works
Self-citationVimaleswaran, K. S., Li, S., Zhao, J. H., Luan, J., Bingham, S. A., Khaw, K.-T., Ekelund, U., Wareham, N. J., & Loos, R. J. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27652 · Cited by 202 · see citing works
Self-citationDayeh, T. A., Olsson, A. H., Volkov, P., Almgren, P., Rönn, T., & Ling, C. (2013) · Diabetologia · doi:10.1007/s00125-012-2815-7 · Cited by 199 · see citing works
Diet-microbiota interactions and their implications for healthy living
Jeffery, I., & O'Toole, P. (2013) · Nutrients · doi:10.3390/nu5010234 · Cited by 199 · see citing works
Genetics of intellectual disability
Ropers, H. H. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.07.008 · Cited by 199 · see citing works
Strausz, S., Ruotsalainen, S., Ollila, H. M., Karjalainen, J., Kiiskinen, T., Reeve, M., Kurki, M., Mars, N., Havulinna, A. S., Luonsi, E., et al. (2021) · European Respiratory Journal · doi:10.1183/13993003.03091-2020 · Cited by 194 · see citing works
- Authors
- Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R. B., Elliott, K. S., Lango, H., Rayner, N. W., Shields, B., Harries, L. W., Barrett, J. C., Ellard, S., Groves, C. J., Knight, B., Patch, A.-M., Ness, A. R., Ebrahim, S., Lawlor, D. A., Ring, S. M., Ben-Shlomo, Y., Jarvelin, M.-R., Sovio, U., Bennett, A. J., Melzer, D., Ferrucci, L., Loos, R. J. F., Barroso, I., Wareham, N. J., Karpe, F., Owen, K. R., Cardon, L. R., Walker, M., Hitman, G. A., Palmer, C. N. A., Doney, A. S. F., Morris, A. D., Smith, G. D., Hattersley, A. T., & McCarthy, M. I.
- Affiliations
- Centre for Human Genetics (GB)
- Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK.
- National Health Service (GB)
- National Institutes of Health (US)
- Corresponding author
- Frayling, Timothy M.
- Timpson, Nicholas J.
- Weedon, Michael N.
- Zeggini, Eleftheria
- Hattersley, Andrew T.
- McCarthy, Mark I.
- ORCID
- Frayling, Timothy M.
- Timpson, Nicholas J.
- Weedon, Michael N.
- Zeggini, Eleftheria
- Freathy, Rachel M.
- Lindgren, Cecilia M.
- Perry, John R. B.
- Elliott, Katherine S.
- Rayner, Nigel W.
- Shields, Beverley
- Harries, Lorna W.
- Barrett, Jeffrey C.
- Ellard, Sian
- Knight, Bridget
- Patch, Ann-Marie
- Ebrahim, Shah
- Lawlor, Debbie A.
- Ring, Susan M.
- Sovio, Ulla
- Bennett, Amanda J.
- Melzer, David
- Ferrucci, Luigi
- Loos, Ruth J. F.
- Wareham, Nicholas J.
- Karpe, Fredrik
- Owen, Katharine R.
- Walker, Mark
- Hitman, Graham A.
- Doney, Alex S. F.
- Morris, Andrew D.
- Smith, George Davey
- Hattersley, Andrew T.
- McCarthy, Mark I.
- Venue
- Science
- Published
- 2007-05-11
- Volume
- 316
- Issue
- 5826
- Pages
- 889-894
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2646098
- OpenAlex
- W2097660065
- Cited by
- 4,531
- References
- 14
- Citations by year
- 2026: 105 · 2025: 154 · 2024: 194 · 2023: 168 · 2022: 196 · 2021: 209 · 2020: 218 · 2019: 180 · 2018: 231 · 2017: 214 · 2016: 236 · 2015: 225 · 2014: 270 · 2013: 315 · 2012: 278
- FWCI
- 191.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (079557, 090532)
- National Institutes of Health (Z99 AG999999)
- Medical Research Council (G0000934, G0600705)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- FTO, fat mass and obesity-associated gene, single nucleotide polymorphisms, body mass index, obesity predisposition, childhood obesity, adult obesity, type 2 diabetes risk, genetic association, fat mass, risk alleles
- MeSH terms
- Adipose Tissue, Adolescent, Adult, Aged, Alleles, Birth Weight, Child, Diabetes Mellitus, Type 2, Female, United Kingdom, Homozygote, Humans, Infant, Newborn, Male, Middle Aged, Obesity, Cohort Studies, Body Mass Index, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Overweight
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
