An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

Simon D. Rees, M. Islam, M. Zafar I. Hydrie, B. Chaudhary, Srikanth Bellary, S. Hashmi, Joseph P. O'Hare, Sudhesh Kumar, D.K. Sanghera, N. Chaturvedi, Anthony H. Barnett, A.S. Shera, M.N. Weedon, Abdul Basit, T M Frayling, M. Ann Kelly, T.H. Jafar

Research output: Contribution to journalArticle

Abstract

Aims - A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.

Methods - We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged = 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies.

Results - In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24–0.67) kg/m2 per A-allele (P = 3.0 × 10-5) and with waist circumference was 0.88 (95% CI 0.36–1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07–1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14–1.31); P = 1.07 × 10-8] even after adjusting for BMI [1.18 (95% CI 1.10–1.27); P = 1.02 × 10-5] or waist circumference [1.18 (95% CI 1.10–1.27); P = 3.97 × 10-5].

Conclusions - The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Original languageEnglish
Pages (from-to)673-680
Number of pages8
JournalDiabetic Medicine
Volume28
Issue number6
Early online date16 May 2011
DOIs
Publication statusPublished - Jun 2011

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Waist Circumference
Type 2 Diabetes Mellitus
Body Mass Index
Alleles
Meta-Analysis
Obesity
Population
Genotype
Population Control
Pakistan
Adiposity
Gene Frequency
Fats
Odds Ratio
Regression Analysis
Blood Pressure
Genes

Bibliographical note

© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Keywords

  • adolescent
  • adult
  • Asian continental ancestry group
  • body mass index
  • cardiovascular diseases
  • type 2 diabetes mellitus
  • diabetic angiopathies
  • female
  • genetic predisposition to disease
  • humans
  • male
  • middle aged
  • obesity
  • single nucleotide polymorphism
  • waist circumference
  • young adult
  • meta-analysis
  • FTO
  • South Asian
  • type 2 diabetes

Cite this

Rees, Simon D. ; Islam, M. ; Hydrie, M. Zafar I. ; Chaudhary, B. ; Bellary, Srikanth ; Hashmi, S. ; O'Hare, Joseph P. ; Kumar, Sudhesh ; Sanghera, D.K. ; Chaturvedi, N. ; Barnett, Anthony H. ; Shera, A.S. ; Weedon, M.N. ; Basit, Abdul ; Frayling, T M ; Kelly, M. Ann ; Jafar, T.H. / An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference. In: Diabetic Medicine. 2011 ; Vol. 28, No. 6. pp. 673-680.
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abstract = "Aims - A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. Methods - We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged = 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. Results - In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95{\%} CI 0.24–0.67) kg/m2 per A-allele (P = 3.0 × 10-5) and with waist circumference was 0.88 (95{\%} CI 0.36–1.41) cm per A-allele (P = 0.001). The A-allele (30{\%} frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95{\%} CI) 1.18 (1.07–1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95{\%} CI 1.14–1.31); P = 1.07 × 10-8] even after adjusting for BMI [1.18 (95{\%} CI 1.10–1.27); P = 1.02 × 10-5] or waist circumference [1.18 (95{\%} CI 1.10–1.27); P = 3.97 × 10-5]. Conclusions - The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.",
keywords = "adolescent, adult, Asian continental ancestry group, body mass index, cardiovascular diseases, type 2 diabetes mellitus, diabetic angiopathies, female, genetic predisposition to disease, humans, male, middle aged, obesity, single nucleotide polymorphism, waist circumference, young adult, meta-analysis, FTO, South Asian, type 2 diabetes",
author = "Rees, {Simon D.} and M. Islam and Hydrie, {M. Zafar I.} and B. Chaudhary and Srikanth Bellary and S. Hashmi and O'Hare, {Joseph P.} and Sudhesh Kumar and D.K. Sanghera and N. Chaturvedi and Barnett, {Anthony H.} and A.S. Shera and M.N. Weedon and Abdul Basit and Frayling, {T M} and Kelly, {M. Ann} and T.H. Jafar",
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Rees, SD, Islam, M, Hydrie, MZI, Chaudhary, B, Bellary, S, Hashmi, S, O'Hare, JP, Kumar, S, Sanghera, DK, Chaturvedi, N, Barnett, AH, Shera, AS, Weedon, MN, Basit, A, Frayling, TM, Kelly, MA & Jafar, TH 2011, 'An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference', Diabetic Medicine, vol. 28, no. 6, pp. 673-680. https://doi.org/10.1111/j.1464-5491.2011.03257.x

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference. / Rees, Simon D.; Islam, M.; Hydrie, M. Zafar I.; Chaudhary, B.; Bellary, Srikanth; Hashmi, S.; O'Hare, Joseph P.; Kumar, Sudhesh; Sanghera, D.K.; Chaturvedi, N.; Barnett, Anthony H.; Shera, A.S.; Weedon, M.N.; Basit, Abdul; Frayling, T M; Kelly, M. Ann; Jafar, T.H.

In: Diabetic Medicine, Vol. 28, No. 6, 06.2011, p. 673-680.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference

AU - Rees, Simon D.

AU - Islam, M.

AU - Hydrie, M. Zafar I.

AU - Chaudhary, B.

AU - Bellary, Srikanth

AU - Hashmi, S.

AU - O'Hare, Joseph P.

AU - Kumar, Sudhesh

AU - Sanghera, D.K.

AU - Chaturvedi, N.

AU - Barnett, Anthony H.

AU - Shera, A.S.

AU - Weedon, M.N.

AU - Basit, Abdul

AU - Frayling, T M

AU - Kelly, M. Ann

AU - Jafar, T.H.

N1 - © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

PY - 2011/6

Y1 - 2011/6

N2 - Aims - A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. Methods - We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged = 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. Results - In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24–0.67) kg/m2 per A-allele (P = 3.0 × 10-5) and with waist circumference was 0.88 (95% CI 0.36–1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07–1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14–1.31); P = 1.07 × 10-8] even after adjusting for BMI [1.18 (95% CI 1.10–1.27); P = 1.02 × 10-5] or waist circumference [1.18 (95% CI 1.10–1.27); P = 3.97 × 10-5]. Conclusions - The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

AB - Aims - A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. Methods - We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged = 40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case–control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. Results - In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95% CI 0.24–0.67) kg/m2 per A-allele (P = 3.0 × 10-5) and with waist circumference was 0.88 (95% CI 0.36–1.41) cm per A-allele (P = 0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95% CI) 1.18 (1.07–1.30); P = 0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95% CI 1.14–1.31); P = 1.07 × 10-8] even after adjusting for BMI [1.18 (95% CI 1.10–1.27); P = 1.02 × 10-5] or waist circumference [1.18 (95% CI 1.10–1.27); P = 3.97 × 10-5]. Conclusions - The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

KW - adolescent

KW - adult

KW - Asian continental ancestry group

KW - body mass index

KW - cardiovascular diseases

KW - type 2 diabetes mellitus

KW - diabetic angiopathies

KW - female

KW - genetic predisposition to disease

KW - humans

KW - male

KW - middle aged

KW - obesity

KW - single nucleotide polymorphism

KW - waist circumference

KW - young adult

KW - meta-analysis

KW - FTO

KW - South Asian

KW - type 2 diabetes

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