Genetic risk variants for metabolic traits in Arab populations

• Published in: Scientific reports 2017-01, Vol.7 (1), p.40988-40988, Article 40988
• Main Authors: Hebbar, Prashantha, Elkum, Naser, Alkayal, Fadi, John, Sumi Elsa, Thanaraj, Thangavel Alphonse, Alsmadi, Osama
• Format: Article
• Language: English
• Subjects: 38/43; 631/208; 631/208/205; Arabs; Ceramide; Fasting; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotyping Techniques; Hemoglobin; Heredity; High density lipoprotein; Humanities and Social Sciences; Insulin-like growth factor I; Kinases; Kuwait; Laboratory testing; MAP kinase; Metabolic Diseases - genetics; Metabolic pathways; Metabolism; multidisciplinary; Otx2 protein; Polymorphism, Single Nucleotide; Population studies; Prevalence; Protein kinase; Science; Science (multidisciplinary); Sequence Analysis, DNA; Single-nucleotide polymorphism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep40988

Despite a high prevalence of metabolic trait related diseases in Arabian Peninsula, there is a lack of convincingly identified genetic determinants for metabolic traits in this population. Arab populations are underrepresented in global genome-wide association studies. We genotyped 1965 unrelated Arab individuals from Kuwait using Cardio-MetaboChip, and tested SNP associations with 13 metabolic traits. Models based on recessive mode of inheritance identified Chr15:40531386-rs12440118/ ZNF106 /W->R as a risk variant associated with glycated-hemoglobin at close to ‘genome-wide significant’ p-value and five other risk variants ‘nominally’ associated (p-value ≤ 5.45E-07) with fasting plasma glucose (rs7144734/[ OTX2-AS1,RPL3P3 ]) and triglyceride (rs17501809/ PLGRKT ; rs11143005/ LOC105376072 ; rs900543/[ THSD4,NR2E3 ]; and Chr12:101494770/ IGF1 ). Furthermore, we identified 33 associations (30 SNPs with 12 traits) with ‘suggestive’ evidence of association (p-value