title: Genetic risk variants for metabolic traits in Arab populations.
abstract: 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 < 1.0E-05); 20 of these operate under recessive mode of inheritance. Two of these 'suggestive' associations (rs1800775-CETP/HDL; and rs9326246-BUD13/TGL) showed evidence at genome-wide significance in previous studies on Euro-centric populations. Involvement of many of the identified loci in mediating metabolic traits was supported by literature evidences. The identified loci participate in critical metabolic pathways (such as Ceramide signaling, and Mitogen-Activated Protein Kinase/Extracellular Signal Regulated Kinase signaling). Data from Genotype-Tissue Expression database affirmed that 7 of the identified variants differentially regulate the up/downstream genes that mediate metabolic traits.
authors.affiliation: Dasman Diabetes Institute, P.O. Box 1180, Dasman 15462, Kuwait.
authors.forename: Prashantha
authors.initials: P
authors.lastname: Hebbar
authors.affiliation: Dasman Diabetes Institute, P.O. Box 1180, Dasman 15462, Kuwait.
authors.forename: Naser
authors.initials: N
authors.lastname: Elkum
authors.affiliation: Dasman Diabetes Institute, P.O. Box 1180, Dasman 15462, Kuwait.
authors.forename: Fadi
authors.initials: F
authors.lastname: Alkayal
authors.affiliation: Dasman Diabetes Institute, P.O. Box 1180, Dasman 15462, Kuwait.
authors.forename: Sumi Elsa
authors.initials: SE
authors.lastname: John
authors.affiliation: Dasman Diabetes Institute, P.O. Box 1180, Dasman 15462, Kuwait.
authors.forename: Thangavel Alphonse
authors.initials: TA
authors.lastname: Thanaraj
authors.affiliation: Dasman Diabetes Institute, P.O. Box 1180, Dasman 15462, Kuwait.
authors.forename: Osama
authors.initials: O
authors.lastname: Alsmadi
mesh_terms: D018912:Arabs; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D007730:Kuwait; D008659:Metabolic Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017422:Sequence Analysis, DNA