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Epigenetic associations of type 2 diabetes and BMI in an Arab population

BACKGROUND: The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these com...

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Autores principales: Al Muftah, Wadha A., Al-Shafai, Mashael, Zaghlool, Shaza B., Visconti, Alessia, Tsai, Pei-Chien, Kumar, Pankaj, Spector, Tim, Bell, Jordana, Falchi, Mario, Suhre, Karsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730771/
https://www.ncbi.nlm.nih.gov/pubmed/26823690
http://dx.doi.org/10.1186/s13148-016-0177-6
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author Al Muftah, Wadha A.
Al-Shafai, Mashael
Zaghlool, Shaza B.
Visconti, Alessia
Tsai, Pei-Chien
Kumar, Pankaj
Spector, Tim
Bell, Jordana
Falchi, Mario
Suhre, Karsten
author_facet Al Muftah, Wadha A.
Al-Shafai, Mashael
Zaghlool, Shaza B.
Visconti, Alessia
Tsai, Pei-Chien
Kumar, Pankaj
Spector, Tim
Bell, Jordana
Falchi, Mario
Suhre, Karsten
author_sort Al Muftah, Wadha A.
collection PubMed
description BACKGROUND: The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigenome-wide association studies (EWASs) have revealed significant associations of T2D, obesity, and BMI with DNA methylation. However, populations from the Middle East, where T2D and obesity rates are highest worldwide, have not been investigated so far. METHODS: We performed the first EWAS in an Arab population with T2D and BMI and attempted to replicate 47 EWAS associations previously reported in Caucasians. We used the Illumina Infinium HumanMethylation450 BeadChip to quantify DNA methylation in whole blood DNA from 123 subjects of 15 multigenerational families from Qatar. To investigate the effect of differing genetic background and environment on the epigenetic associations, we further assessed the effect of replicated loci in 810 twins from UK. RESULTS: Our EWAS suggested a novel association between T2D and cg06721411 (DQX1; p value = 1.18 × 10(−9)). We replicated in the Qatari population seven CpG associations with BMI (SOCS3, p value = 3.99 × 10(−6); SREBF1, p value = 4.33 × 10(−5); SBNO2, p value = 5.87 × 10(−5); CPT1A, p value = 7.99 × 10(−5); PRR5L, p value = 1.85 × 10(−4); cg03078551, intergenic region on chromosome 17; p value = 1.00 × 10(−3); LY6G6E, p value = 1.10 × 10(−3)) and one with T2D (TXNIP, p value = 2.46 × 10(−5)). All the associations were further confirmed in the UK cohort for both BMI and T2D. Meta-analysis increased the significance of the observed associations and revealed strong heterogeneity of the effect sizes (apart from CPT1A), although associations at these loci showed concordant direction in the two populations. CONCLUSIONS: Our study replicated eight known CpG associations with T2D or BMI in an Arab population. Heterogeneity of the effects at all loci except CPT1A between the Qatari and UK studies suggests that the underlying mechanisms might depend on genetic background and environmental pressure. Our EWAS results provide a basis for comparison with other ethnicities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0177-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-47307712016-01-29 Epigenetic associations of type 2 diabetes and BMI in an Arab population Al Muftah, Wadha A. Al-Shafai, Mashael Zaghlool, Shaza B. Visconti, Alessia Tsai, Pei-Chien Kumar, Pankaj Spector, Tim Bell, Jordana Falchi, Mario Suhre, Karsten Clin Epigenetics Research BACKGROUND: The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigenome-wide association studies (EWASs) have revealed significant associations of T2D, obesity, and BMI with DNA methylation. However, populations from the Middle East, where T2D and obesity rates are highest worldwide, have not been investigated so far. METHODS: We performed the first EWAS in an Arab population with T2D and BMI and attempted to replicate 47 EWAS associations previously reported in Caucasians. We used the Illumina Infinium HumanMethylation450 BeadChip to quantify DNA methylation in whole blood DNA from 123 subjects of 15 multigenerational families from Qatar. To investigate the effect of differing genetic background and environment on the epigenetic associations, we further assessed the effect of replicated loci in 810 twins from UK. RESULTS: Our EWAS suggested a novel association between T2D and cg06721411 (DQX1; p value = 1.18 × 10(−9)). We replicated in the Qatari population seven CpG associations with BMI (SOCS3, p value = 3.99 × 10(−6); SREBF1, p value = 4.33 × 10(−5); SBNO2, p value = 5.87 × 10(−5); CPT1A, p value = 7.99 × 10(−5); PRR5L, p value = 1.85 × 10(−4); cg03078551, intergenic region on chromosome 17; p value = 1.00 × 10(−3); LY6G6E, p value = 1.10 × 10(−3)) and one with T2D (TXNIP, p value = 2.46 × 10(−5)). All the associations were further confirmed in the UK cohort for both BMI and T2D. Meta-analysis increased the significance of the observed associations and revealed strong heterogeneity of the effect sizes (apart from CPT1A), although associations at these loci showed concordant direction in the two populations. CONCLUSIONS: Our study replicated eight known CpG associations with T2D or BMI in an Arab population. Heterogeneity of the effects at all loci except CPT1A between the Qatari and UK studies suggests that the underlying mechanisms might depend on genetic background and environmental pressure. Our EWAS results provide a basis for comparison with other ethnicities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-016-0177-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-28 /pmc/articles/PMC4730771/ /pubmed/26823690 http://dx.doi.org/10.1186/s13148-016-0177-6 Text en © Al Muftah et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Al Muftah, Wadha A.
Al-Shafai, Mashael
Zaghlool, Shaza B.
Visconti, Alessia
Tsai, Pei-Chien
Kumar, Pankaj
Spector, Tim
Bell, Jordana
Falchi, Mario
Suhre, Karsten
Epigenetic associations of type 2 diabetes and BMI in an Arab population
title Epigenetic associations of type 2 diabetes and BMI in an Arab population
title_full Epigenetic associations of type 2 diabetes and BMI in an Arab population
title_fullStr Epigenetic associations of type 2 diabetes and BMI in an Arab population
title_full_unstemmed Epigenetic associations of type 2 diabetes and BMI in an Arab population
title_short Epigenetic associations of type 2 diabetes and BMI in an Arab population
title_sort epigenetic associations of type 2 diabetes and bmi in an arab population
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730771/
https://www.ncbi.nlm.nih.gov/pubmed/26823690
http://dx.doi.org/10.1186/s13148-016-0177-6
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