title: Epigenetic associations of type 2 diabetes and BMI in an Arab population.
abstract: 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.
authors.affiliation: Bioinformatics Core, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.|Department of Genomics of Common Disease, Imperial College London, London, UK.|Research Division, Qatar Science Leadership Program, Qatar Foundation, Doha, Qatar.
authors.forename: Wadha A
authors.initials: WA
authors.lastname: Al Muftah
authors.affiliation: Bioinformatics Core, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.|Department of Genomics of Common Disease, Imperial College London, London, UK.|Research Division, Qatar Science Leadership Program, Qatar Foundation, Doha, Qatar.
authors.forename: Mashael
authors.initials: M
authors.lastname: Al-Shafai
authors.affiliation: Bioinformatics Core, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.
authors.forename: Shaza B
authors.initials: SB
authors.lastname: Zaghlool
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH UK.
authors.forename: Alessia
authors.initials: A
authors.lastname: Visconti
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH UK.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Bioinformatics Core, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Spector
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH UK.
authors.forename: Jordana
authors.initials: J
authors.lastname: Bell
authors.affiliation: Department of Genomics of Common Disease, Imperial College London, London, UK.|Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH UK.
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.affiliation: Bioinformatics Core, Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, PO Box 24144, Doha, Qatar.|Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH UK.|Helmholtz Zentrum München, Research Center for Environmental Health, 85764 Neuherberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018912:Arabs / Q000235:genetics*; D015992:Body Mass Index; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011780:Qatar / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
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