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A common genetic variant is associated with adult and childhood obesity.
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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“To limit the conundrum of multiple testing, we used a more stringent criteria for SNP selection in the second sample[39]. Subjects were genotyped solely for the three SNPs found to be significant in both the SVO and Dictator in the first sample (rs2268490, rs237887 and rs1042778).”
From The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task (2009) · cites this paper as [39]
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“Originally, a variant (rs7566605) within the insulininduced gene 2 (INSIG2) was associated with increased risk of obesity in some but not all studies (Herbert et al., 2006; Lyon et al., 2007; Smith et al., 2007; Hubáček et al., 2010).”
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“The availability of low-cost, high-throughput technologies for genotyping hundreds of thousands of DNA markers has led to a number of successes in identifying associations between these markers and complex traits like age-related macular degeneration [1‐3], diabetes [4, 5], and obesity [ 6 ], validating the GWAS appro…”
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“In human, several studies found that INSIG-2 genetic polymorphisms are associated with weight gain, obesity and hypercholesterolemia [10].”
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“We also evaluated the rs7566605 genotype located near the INSIG2 gene.(12) Genotyping of the G→C SNP (rs7566605) was performed with the primers rs7566605-F (AGTAGGGTGAGGAAACCAAATTCTC) and rs7566605-R (CATGACCCCTACCGTCTCTATTTT), and the probes rs7566605-VIC (ACAGAGATGTTA CATCAC labeled with the dye VIC) and rs7566605FA…”
BackgroundMethodGenomewide Association Studies
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“Association of the SNP rs7566605 and weight gain was first seen in related individuals from the Framingham Heart Study (18) where the authors went on to speculate that the SNP rs7566605 may affect regulation of the gene in closest proximity: insulin-induced gene 2 (INSIG2 ; (18,19)).”
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2015 ASHG Awards and Addresses
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Nutrition and Diet in the Era of Genomics
Ordovás, J. M., & Corella, D. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-369420-1.00098-6 · Cited by 2
Identification of leptin gene variants in school children with early onset obesity.
Kongmacheep, P., Sirikulchayanonta, C., Tungtrongchitr, R., & Hancharoen, K. (2009) · PubMed · Cited by 2
Hollenrieder, V. (2017) · Springer eBooks · doi:10.1007/978-3-662-53058-0_5 · Cited by 2
Application of Genetic Epidemiology to Understanding Pediatric Obesity
Mair, R. D., & McGarvey, S. T. (2008) · Issues in clinical child psychology · doi:10.1007/978-0-387-76924-0_11 · Cited by 2
Genome-Wide Association Studies of Obesity
Hedman, Å. K., Lindgren, C. M., & McCarthy, M. I. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8642-8_3 · Cited by 2
Bedeutung der Genetik beim Thema "soziale Ungleichheit und Gesundheit"
Mielck, A., & Rogowski, W. H. (2007) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-007-0139-4 · Cited by 2
Concerns over 'shifting sands' linger as genetic testing expands
Khamsi, R. (2008) · Nature Medicine · doi:10.1038/nm0608-589 · Cited by 2
Mankind adaptation and present human health
Contaldo, F., & Auricchio, S. (2008) · Internal and Emergency Medicine · doi:10.1007/s11739-008-0171-x · Cited by 2
Quantitative Trait Loci Mapping
Xiong, D.-H., Liu, J., Guo, Y.-F., Guo, Y., Yang, T., Jiang, H., Chen, Y., Yang, F., Recker, R. R., & Deng, H. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-104-8_16 · Cited by 3
Evolutionary origins of diversity in human viruses
Sharp, P. M., Bailes, E., & Wain, L. V. (2007) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199207466.003.0013 · Cited by 2
Eating Behaviors in Obesity: The Role of Appetite
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PhD, T. C. S. M., & PhD, B. S. M. (2015) · AIMS Public Health · doi:10.3934/publichealth.2015.3.487 · Cited by 1
“Numerous efforts are underway to identify genetic predispositions even while other research suggests the environment to be as likely an influential factor in childhood or adolescent obesity [22,27,28].”
BackgroundGenetics of Nonsyndromic Human Obesity, With Suggestions for New Studies From Work in Mouse Models
Warden, C. H., & Fisler, J. S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802928-2.00021-7 · Cited by 1
Association of common genetic variants with body mass index in Russian population
Berseneva, A. A., Kovalenko, E. V., Vergasova, E., Prohorov, A., Popov, I., Ilinskaya, A. Y., Kim, A., Plotnikov, N. A., Elmuratov, A. U., Ilinsky, V. V., et al. (2023) · European Journal of Clinical Nutrition · doi:10.1038/s41430-023-01265-z · Cited by 1
“[13] on BMI identified a variant in the INSIG2 (insulin-induced gene 2), which, however, did not reach the whole genome significance and was not identified in either [14–17] or in further wholegenome studies.”
BackgroundDas nationale Genomforschungsnetz
Bickeböller, H. (2007) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-007-0137-6 · Cited by 1
“Die Forschergruppe um Professor Johannes Hebebrand und Anke Hinney (Universität Duisburg-Essen) verbindet den Ansatz der Positionsklonierung mit Methoden der genetischen Epidemiologie, um Gene für Fettleibigkeit (Adipositas) aufzuspüren [13, 14, 15, 16].”
BackgroundPrice, R. A. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1607-5_7 · Cited by 1
“The first few had relatively low genome coverage and found no associations that met a genome-wide level of significance (2 × 10 –7 ) [28, 29 ].”
Background
Metadata
- 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
- Venue
- Science
- Published
- 2006-04-14
- Volume
- 312
- Issue
- 5771
- Pages
- 279-283
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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