Genetic risk variants for metabolic traits in Arab populations

Prashantha Hebbar, Naser Elkum, Fadi Alkayal, Sumi Elsa John, Thangavel Alphonse Thanaraj, Osama Alsmadi

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 â € genome-wide significant' p-value and five other risk variants â € 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 â € suggestive' evidence of association (p-value < 1.0E-05); 20 of these operate under recessive mode of inheritance. Two of these â € 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.

Original languageEnglish
Article number40988
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 20 Jan 2017
Externally publishedYes

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Single Nucleotide Polymorphism
Genome
Population
Kuwait
Critical Pathways
Ceramides
Genome-Wide Association Study
Extracellular Signal-Regulated MAP Kinases
Glycosylated Hemoglobin A
Metabolic Networks and Pathways
Mitogen-Activated Protein Kinases
Fasting
Triglycerides
Genotype
Databases
Glucose
Genes

ASJC Scopus subject areas

  • General

Cite this

Hebbar, P., Elkum, N., Alkayal, F., John, S. E., Thanaraj, T. A., & Alsmadi, O. (2017). Genetic risk variants for metabolic traits in Arab populations. Scientific Reports, 7, [40988]. https://doi.org/10.1038/srep40988

Genetic risk variants for metabolic traits in Arab populations. / Hebbar, Prashantha; Elkum, Naser; Alkayal, Fadi; John, Sumi Elsa; Thanaraj, Thangavel Alphonse; Alsmadi, Osama.

In: Scientific Reports, Vol. 7, 40988, 20.01.2017.

Research output: Contribution to journalArticle

Hebbar, P, Elkum, N, Alkayal, F, John, SE, Thanaraj, TA & Alsmadi, O 2017, 'Genetic risk variants for metabolic traits in Arab populations', Scientific Reports, vol. 7, 40988. https://doi.org/10.1038/srep40988
Hebbar, Prashantha ; Elkum, Naser ; Alkayal, Fadi ; John, Sumi Elsa ; Thanaraj, Thangavel Alphonse ; Alsmadi, Osama. / Genetic risk variants for metabolic traits in Arab populations. In: Scientific Reports. 2017 ; Vol. 7.
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