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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“snP selection and genetic analyses The SNP rs7566605 located near the INSIG2 gene (Figure 1) was selected due to its association with obesity in several studies (5,6).”
BackgroundResultInfluential
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“E-mail: richard.neapolitan@northwestern.edu 150 risk loci associated with 60 common diseases and traits [Herbert et al., 2006; Lambert, 2009; Manolio and Collins, 2009; Spinola et al., 2001].”
Background
Linkage analysis of obesity phenotypes in pre- and post-menopausal women from a United States mid-western population
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BackgroundInfluential
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“Herbert et al (19) reported that a common variant (rs7566605) located 10 kb upstream of insulin-induced gene 2 (INSIG2) was associated with obesity.”
Background
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Background
Controversial association results for INSIG2 on body mass index may be explained by interactions with age and with MC4R
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Background
No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits
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On Quality Control Measures in Genome-Wide Association Studies: A Test to Assess the Genotyping Quality of Individual Probands in Family-Based Association Studies and an Application to the HapMap Data
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The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk
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BackgroundInfluential
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“Among them 2 polymorphisms were found in the vicinity of the FTO (fat mass and obesity associated) and INSIG2 (insulin-induced gene 2) genes [Herbert et al., 2006; Frayling et al., 2007].”
Background
The association of a SNP upstream of INSIG2 with Body Mass Index is reproduced in several but not all cohorts
Lyon, H. N., Emilsson, V., Hinney, A., Heid, I. M., Lasky-Su, J. A., Zhu, X., Þorleifsson, G., Gunnarsdottir, S., Walters, G. B., Þorsteinsdóttir, U., et al. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0030061.eor · Cited by 10
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Genetic associations of the INSIG2 rs7566605 polymorphism with obesity-related metabolic traits in Malaysian Malays
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Method
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Vehof, J., Hadithy, A. F. Y. A., Burger, H., Snieder, H., Risselada, A., Wilffert, B., Cohen, D., Arends, J., Wiersma, D., Mulder, H., et al. (2011) · Psychiatric Genetics · doi:10.1097/ypg.0b013e3283458a51 · Cited by 9
“In a recent reanalysis of a scan of 86 604 single nucleotide polymorphisms (SNPs) among 1322 individuals in the Framingham Heart study offspring cohort [for the original analysis, see Herbert et al. (2006)] Lasky-Su et al.”
Background
Shared ancestral susceptibility to colorectal cancer and other nutrition related diseases
Huhn, S., Bevier, M., Rudolph, A., Pardini, B., Naccarati, A., Hein, R., Hoffmeister, M., Vodičková, L., Novotný, J. P., Brenner, H., et al. (2012) · BMC Medical Genetics · doi:10.1186/1471-2350-13-94 · Cited by 8
“280 AG D T2D GPR45 ~20kb down [17] Chr 11 gap rs9300039 11p12.”
Open-access database of candidate associations from a genome-wide SNP scan of the Framingham Heart Study
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Influential
Response to Comments on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
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Result

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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