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; DIAGRAM Consortium; F. Pellegrini; L. Mercuri; D. Bailetti; N. Abate; L. Frittitta; G. Sesti; J. C. Florez; A. Doria; V. Trischitta

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 (Lead / Corresponding author), M. Copetti, E. Morini, C. Mendonca, F. Andreozzi, M. Chandalia, R. Baratta, DIAGRAM Consortium, F. Pellegrini, L. Mercuri, D. Bailetti, N. Abate, L. Frittitta, G. Sesti, J. C. Florez, A. Doria, V. Trischitta (Lead / Corresponding author)

Research output: Contribution to journal › Article › peer-review

5 Citations (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.

Original language	English
Pages (from-to)	1043-1049
Number of pages	7
Journal	Nutrition, Metabolism and Cardiovascular Diseases
Volume	23
Issue number	11
DOIs	https://doi.org/10.1016/j.numecd.2013.05.001
Publication status	Published - Nov 2013

Keywords

Adaptor Proteins, Signal Transducing
Adult
European Continental Ancestry Group
Evidence-Based Medicine
Genetic Association Studies
Genetic Loci
Glucose Metabolism Disorders
Humans
Obesity
Polymorphism, Single Nucleotide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.numecd.2013.05.001

Cite this

Prudente, S., Copetti, M., Morini, E., Mendonca, C., Andreozzi, F., Chandalia, M., Baratta, R., DIAGRAM Consortium, Pellegrini, F., Mercuri, L., Bailetti, D., Abate, N., Frittitta, L., Sesti, G., Florez, J. C., Doria, A., & Trischitta, V. (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 and Cardiovascular Diseases, 23(11), 1043-1049. https://doi.org/10.1016/j.numecd.2013.05.001

@article{e142d42ce6614782b78c42cd43a138e7,

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.",

keywords = "Adaptor Proteins, Signal Transducing, Adult, European Continental Ancestry Group, Evidence-Based Medicine, Genetic Association Studies, Genetic Loci, Glucose Metabolism Disorders, Humans, Obesity, Polymorphism, Single Nucleotide",

author = "S. Prudente and M. Copetti and E. Morini and C. Mendonca and F. Andreozzi and M. Chandalia and R. Baratta and {DIAGRAM Consortium} 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 Palmer, {Colin Neil Alexander}",

year = "2013",

month = nov,

doi = "10.1016/j.numecd.2013.05.001",

language = "English",

volume = "23",

pages = "1043--1049",

journal = "Nutrition, Metabolism and Cardiovascular Diseases",

issn = "0939-4753",

publisher = "Elsevier",

number = "11",

}

Prudente, S, Copetti, M, Morini, E, Mendonca, C, Andreozzi, F, Chandalia, M, Baratta, R, DIAGRAM Consortium, Pellegrini, F, Mercuri, L, Bailetti, D, Abate, N, Frittitta, L, Sesti, G, Florez, JC, Doria, A & Trischitta, V 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 and Cardiovascular Diseases, vol. 23, no. 11, pp. 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. (Lead / Corresponding author); Copetti, M.; Morini, E. et al.
In: Nutrition, Metabolism and Cardiovascular Diseases, Vol. 23, No. 11, 11.2013, p. 1043-1049.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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 - DIAGRAM Consortium

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 - Palmer, Colin Neil Alexander

PY - 2013/11

Y1 - 2013/11

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.

KW - Adaptor Proteins, Signal Transducing

KW - Adult

KW - European Continental Ancestry Group

KW - Evidence-Based Medicine

KW - Genetic Association Studies

KW - Genetic Loci

KW - Glucose Metabolism Disorders

KW - Humans

KW - Obesity

KW - Polymorphism, Single Nucleotide

U2 - 10.1016/j.numecd.2013.05.001

DO - 10.1016/j.numecd.2013.05.001

M3 - Article

C2 - 24103803

SN - 0939-4753

VL - 23

SP - 1043

EP - 1049

JO - Nutrition, Metabolism and Cardiovascular Diseases

JF - Nutrition, Metabolism and Cardiovascular Diseases

IS - 11

ER -

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

Abstract

Keywords

UN SDGs

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