Cited by 732Genetic Associations and EpidemiologyGenetics and Physical PerformanceNutrition, Genetics, and Disease

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A common genetic variant is associated with adult and childhood obesity.

Herbert, Alan, Gerry, Norman P., McQueen, Matthew B., Heid, Iris M., Pfeufer, Arne, Illig, Thomas, Wichmann, H.-Erich, Meitinger, Thomas, Hunter, David, Hu, Frank B., Colditz, Graham, Hinney, Anke, Hebebrand, Johannes, Koberwitz, Kerstin, Zhu, Xiaofeng, Cooper, Richard, Ardlie, Kristin, Lyon, Helen, Hirschhorn, Joel N., Laird, Nan M., Lenburg, Marc E., Lange, Christoph, Christman, Michael F.·2006·Science

DOI 10.1126/science.1124779

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Abstract

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.

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BackgroundInfluential
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BackgroundInfluential
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Background
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Method
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Method
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BackgroundMethodInfluential
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Background
Environmental and Genetic Risk Factors in Obesity
Hebebrand, J., & Hinney, A. (2008) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2008.07.006 · Cited by 162
Meta‐Analysis of Genome‐wide Linkage Studies in BMI and Obesity
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“Similarly, the GSMA would miss common genes with a low sibling recurrence risk that would be easily detectable in large association studies, such as the insulininduced gene 2 (INSIG2) gene, which was recently identified as a probable susceptibility gene for obesity by genome-wide association (63).”
Background
Precision Health: The Role of the Social and Behavioral Sciences in Advancing the Vision
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Meta‐Analysis Methods
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Genetic dissection of type 2 diabetes
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BackgroundInfluential
Recent progress in the genetics of common obesity
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Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study
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“From GWAS, several previously unrecognized genes have been identified that may contribute to disease, including CFH and age-related macular degeneration [16], INSIG2 and obesity [17], NOS1AP with QT interval variation [18], and several genes including TCF7L2 [19] as well as IGF2BP2 and CDKA1 with diabetes mellitus [20…”
Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population
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On the Replication of Genetic Associations: Timing Can Be Everything!
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“Details of the significant association between rs7566605 and obesity were described in the previous report.(9) SNP rs1455832 is also common (minor allele frequency [MAF] 1⁄4 0.”
BackgroundMethodInfluential
Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population
Shen, G.-Q., Rao, S., Martinelli, N., Li, L., Olivieri, O., Corrocher, R., Abdullah, K. G., Hazen, S. L., Smith, J. D., Barnard, J., et al. (2007) · Journal of Human Genetics · doi:10.1007/s10038-007-0230-6 · Cited by 133
ARG1 Is a Novel Bronchodilator Response Gene
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Genome-wide association with select biomarker traits in the Framingham Heart Study
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“Acknowledgements The investigators would like to express their gratitude to the Framingham Heart Study participants and key collaborators: Fox CS, Jacques PF, Lee DS, Lipinska I, Massaro JM, Murabito JM, O'Donnell CJ, Seshadri S, Yang Q.”
Influential
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
Christian Dina, C., Meyre, D., Samson, C., Tichet, J., Marre, M., Jouret, B., Charles, M.-A. A., Balkau, B., & Froguel, P. (2007) · Science · doi:10.1126/science.1129402 · Cited by 125
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Linkage Disequilibrium in Wild Mice
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Background
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“Publicly available genome-wide datasets do not reveal any association of 21 FDFT1 variants and apoB, LDL-C or TC (Table 2) (81, 82).”
Background
Contribution of Common Genetic Variants to Obesity and Obesity-Related Traits in Mexican Children and Adults
León‐Mimila, P., Villamil‐Ramírez, H., Villalobos‐Comparán, M., Villarreal-Molina, M. T., Romero‐Hidalgo, S., López-Contreras, B. E., Gutiérrez‐Vidal, R., Vega‐Badillo, J., Jacobo‐Albavera, L., Posadas‐Romero, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070640 · Cited by 123
“[12], we found that the G and not the C allele confers risk for obesity.”
Background
Genetic Determinants of Childhood Obesity
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Khoury, M. J., Little, J., GWINN, M. L., & Ioannidis, J. P. A. (2006) · International Journal of Epidemiology · doi:10.1093/ije/dyl253 · Cited by 119
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“For example, in the cases of obesity and asthma, the first and best-replicated GWAS discoveries, FTO for obesity and the ORMDL3/GSDMB locus on chromosome 17 for asthma, were unanticipated in existing biological models of disease pathogenesis (Herbert et al. 2006; Moffatt et al. 2007).”
Background
Genetics of fat tissue accumulation in pigs: a comparative approach
Switonski, M., Stachowiak, M., Cieślak, J., Bartz, M., & Grzes, M. (2010) · Journal of Applied Genetics · doi:10.1007/bf03195724 · Cited by 116
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
Loos, R. J. F., Barroso, I., O’Rahilly, S., & Wareham, N. J. (2007) · Science · doi:10.1126/science.1130012 · Cited by 115
Evaluation of coverage variation of SNP chips for genome-wide association studies
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The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing, China
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“Several promising genes have been reported to be associated with a variation in body mass index (BMI) in a monogenic or polygenic manner: proprotein convertase subtilisin/kexin type 1 (PCSK1) [6], melanocortin 4 receptor (MC4R) [7], catenin beta-like 1 (CTNNBL1) [8], ectonucleotide pyrophosphatase 1 (ENPP1) [9], and b…”
Background
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
Rosskopf, D., Bornhorst, A., Rimmbach, C., Schwahn, C., Kayser, A., Krüger, A., Tessmann, G., Geissler, I., Kroemer, H. K., & Völzke, H. (2007) · Science · doi:10.1126/science.1130571 · Cited by 112
Molecular genetic studies of gene identification for sarcopenia
Tan, L., Liu, S., Lei, S., Papasian, C. J., & Deng, H. (2011) · Human Genetics · doi:10.1007/s00439-011-1040-7 · Cited by 115
“The GWA approach has successfully identified new variants underlying several complex diseases or traits, such as diabetes (Smyth et al. 2006), obesity (Herbert et al. 2006), osteoporosis (Xiong et al. 2009) and hypertension (Wang et al. 2009b).”
Method
The success of the genome-wide association approach: a brief story of a long struggle
Seng, K. C., & Seng, C. K. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.12 · Cited by 111
Gene–environment interactions and obesity—Further aspects of genomewide association studies
Andreasen, C. H., & Andersen, G. (2009) · Nutrition · doi:10.1016/j.nut.2009.06.001 · Cited by 107
“The first obesity variant to be identified through the GWA approach was located w10 kb upstream of insulin-induced gene-2 (INSIG2) [14]; however, several independent attempts to validate the impact of this variant have been contradictory in their findings [15–19].”
BackgroundResult
Assessing gene–treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program
Franks, P. W., Jablonski, K. A., Delahanty, L. M., McAteer, J. B., Kahn, S. E., Knowler, W. C., & Florez, J. C. (2008) · Diabetologia · doi:10.1007/s00125-008-1158-x · Cited by 106
“Although several subsequent confirmatory analyses were published [11], others found no evidence of association [12–16].”
BackgroundInfluential
A Genome-wide Study Reveals Copy Number Variants Exclusive to Childhood Obesity Cases
Glessner, J., Bradfield, J. P., Wang, K., Takahashi, N., Zhang, H., Abou‐Sleiman, P. M., Mentch, F. D., Kim, C., Hou, C., Thomas, K., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.09.014 · Cited by 105
FTO and MC4R Gene Variants Are Associated with Obesity in Polycystic Ovary Syndrome
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“A total of 15 SNPs associated with obesity that were genotyped are located in or near FTO (rs1421085, rs17817449, rs8050136, rs9939609 and rs9930506) [9,10,16], GNPDA2 (rs10938397), KCTD15 (rs11084753), MTCH2 (rs10838738), NEGR1 (rs2815752), SH2B1 (rs7498665), TMEM18 (rs6548238) [9], MC4R (rs17782313 and rs12970134) […”
Hidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics?
Munawar, N., Ahsan, K., Muhammad, K., Ahmad, A., Anwar, M. A., Shah, I., Ameri, A. A., & Mughairbi, F. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147671 · Cited by 107

Authors: 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., Colditz, G., Hinney, A., Hebebrand, J., Koberwitz, K., Zhu, X., Cooper, R., Ardlie, K., Lyon, H., Hirschhorn, J. N., Laird, N. M., Lenburg, M. E., Lange, C., & Christman, M. F.
Affiliations: Boston University (US)
Corresponding author: Herbert, Alan
Christman, Michael F.
ORCID: Herbert, Alan
McQueen, Matthew B.
Heid, Iris M.
Wichmann, H.-Erich
Meitinger, Thomas
Hu, Frank B.
Colditz, Graham
Hinney, Anke
Hebebrand, Johannes
Zhu, Xiaofeng
Cooper, Richard
Ardlie, Kristin
Hirschhorn, Joel N.
Laird, Nan M.
Lenburg, Marc E.
Lange, Christoph
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2006-04-14
Volume: 312
Issue: 5771
Pages: 279-283
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1124779
OpenAlex: W2149512324
Cited by: 732
References: 32
Citations by year: 2026: 2 · 2025: 5 · 2024: 2 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 2 · 2017: 17 · 2016: 19 · 2015: 28 · 2014: 30 · 2013: 37 · 2012: 39
FWCI: 75.55
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Civil War Book Review (submittedVersion)
mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Site cant be reached (submittedVersion)
Funders: National Heart, Lung, and Blood Institute (R01 HL54485, U01HL065899, R01HL066289, R01HL66289, R01HL074166, U01 HL65899)
National Institute of Mental Health (R01MH59532, R01MH059532)
National Cancer Institute (CA-87969, P01CA087969)
National Institute of General Medical Sciences (R01GM046877)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200, K23DK067288, P30 DK-46200)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD060726)
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: obesity, genetic association, INSIG2, childhood obesity, adult obesity, type 2 diabetes risk, whole genome scan, Framingham Heart Study, African Americans
MeSH terms: Adult, Alleles, Black or African American, Child, Europe, Female, Gene Frequency, Genes, Recessive, Genotype, Haplotypes, Humans, Male, Membrane Proteins, Models, Genetic, Obesity, Genetic Variation, Cohort Studies, Linkage Disequilibrium, Body Mass Index, Case-Control Studies, Genetic Predisposition to Disease, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, White People, Intracellular Signaling Peptides and Proteins

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A common genetic variant is associated with adult and childhood obesity.

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