The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry

S Prudente; M Copetti; E Morini; C Mendonca; F Andreozzi; M Chandalia; R Baratta; F Pellegrini; L Mercuri; D Bailetti; N Abate; L Frittitta; G Sesti; J C Florez; A Doria; V Trischitta; DIAGRAM consortium; Torben Jørgensen

doi:10.1016/j.numecd.2013.05.001

The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry

S Prudente, M Copetti, E Morini, C Mendonca, F Andreozzi, M Chandalia, R Baratta, F Pellegrini, L Mercuri, D Bailetti, N Abate, L Frittitta, G Sesti, J C Florez, A Doria, V Trischitta, DIAGRAM consortium, Torben Jørgensen

5 Citationer (Scopus)

Abstract

Background/Aims: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. Methods: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n=47,117) and four other published studies (n=39,448). Results: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR)=0.96; 0.89-1.04) or in the meta-analysis (OR=1.01; 0.98-1.05). Conclusion: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

Originalsprog	Udefineret/Ukendt
Tidsskrift	Nutrition, Metabolism & Cardiovascular Diseases
Vol/bind	23
Udgave nummer	11
Sider (fra-til)	1043–1049
Antal sider	7
ISSN	0939-4753
DOI	https://doi.org/10.1016/j.numecd.2013.05.001
Status	Udgivet - 1 nov. 2013

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10.1016/j.numecd.2013.05.001

Citationsformater

Prudente, S., Copetti, M., Morini, E., Mendonca, C., Andreozzi, F., Chandalia, M., Baratta, R., Pellegrini, F., Mercuri, L., Bailetti, D., Abate, N., Frittitta, L., Sesti, G., Florez, J. C., Doria, A., Trischitta, V., consortium, DIAGRAM., & Jørgensen, T. (2013). The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry. Nutrition, Metabolism & Cardiovascular Diseases, 23(11), 1043–1049. https://doi.org/10.1016/j.numecd.2013.05.001

The SH2B1 obesity locus and abnormal glucose homeostasis : Lack of evidence for association from a meta-analysis in individuals of European ancestry. / Prudente, S; Copetti, M; Morini, E et al.

I: Nutrition, Metabolism & Cardiovascular Diseases, Bind 23, Nr. 11, 01.11.2013, s. 1043–1049.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Prudente, S, Copetti, M, Morini, E, Mendonca, C, Andreozzi, F, Chandalia, M, Baratta, R, Pellegrini, F, Mercuri, L, Bailetti, D, Abate, N, Frittitta, L, Sesti, G, Florez, JC, Doria, A, Trischitta, V, consortium, DIAGRAM & Jørgensen, T 2013, 'The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry', Nutrition, Metabolism & Cardiovascular Diseases, bind 23, nr. 11, s. 1043–1049. https://doi.org/10.1016/j.numecd.2013.05.001

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title = "The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry",

abstract = "Background/Aims: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. Methods: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n=47,117) and four other published studies (n=39,448). Results: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR)=0.96; 0.89-1.04) or in the meta-analysis (OR=1.01; 0.98-1.05). Conclusion: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.",

author = "S Prudente and M Copetti and E Morini and C Mendonca and F Andreozzi and M Chandalia and R Baratta and F Pellegrini and L Mercuri and D Bailetti and N Abate and L Frittitta and G Sesti and Florez, {J C} and A Doria and V Trischitta and DIAGRAM consortium and Torben J{\o}rgensen",

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T1 - The SH2B1 obesity locus and abnormal glucose homeostasis

T2 - Lack of evidence for association from a meta-analysis in individuals of European ancestry

AU - Prudente, S

AU - Copetti, M

AU - Morini, E

AU - Mendonca, C

AU - Andreozzi, F

AU - Chandalia, M

AU - Baratta, R

AU - Pellegrini, F

AU - Mercuri, L

AU - Bailetti, D

AU - Abate, N

AU - Frittitta, L

AU - Sesti, G

AU - Florez, J C

AU - Doria, A

AU - Trischitta, V

AU - consortium, DIAGRAM

AU - Jørgensen, Torben

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Background/Aims: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. Methods: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n=47,117) and four other published studies (n=39,448). Results: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR)=0.96; 0.89-1.04) or in the meta-analysis (OR=1.01; 0.98-1.05). Conclusion: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

AB - Background/Aims: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. Methods: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n=47,117) and four other published studies (n=39,448). Results: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR)=0.96; 0.89-1.04) or in the meta-analysis (OR=1.01; 0.98-1.05). Conclusion: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

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DO - 10.1016/j.numecd.2013.05.001

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JO - Nutrition, Metabolism & Cardiovascular Diseases

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