The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related traits and mediates by interacting with Apo-A1

Prashantha Hebbar, Fadi Alkayal, Rasheeba Nizam, Motasem Melhem, Naser Elkum, Sumi Elsa John, Mohamed Abufarha, Osama Alsmadi, Thangavel Alphonse Thanaraj

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits. Methods: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome-wide association tests for obesity-related anthropometric traits were performed. Top associations were tested for replication in an independent cohort (1,176 unrelated Arabs). Resultant variants were investigated for interactions with obesity-related plasma biomarkers. Pathway analysis was performed on genes harboring markers in linkage disequilibrium (LD) with identified variants. Results: The rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist circumference (WC) at nearly genome-wide significance (P = 8.92E−08). WC was inversely related with Apo-A1 or high-density lipoprotein levels; individuals with the AG genotype exhibited stronger relationship than those with the reference AA genotype. Interaction involving the AG genotype (effect allele = G) significantly contributed to an increase in anthropometric traits (particularly WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped onto an interaction network (with TP53 as central element) of established obesity/diabetes-related protein components. Conclusions: The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.

Original languageEnglish
Pages (from-to)1098-1108
Number of pages11
JournalObesity
Volume25
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

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Apolipoprotein A-I
Obesity
Waist Circumference
Genotype
Linkage Disequilibrium
HDL Lipoproteins
Genome
Kuwait
Genome-Wide Association Study
Population
Genes
Single Nucleotide Polymorphism
Biomarkers
Alleles

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related traits and mediates by interacting with Apo-A1. / Hebbar, Prashantha; Alkayal, Fadi; Nizam, Rasheeba; Melhem, Motasem; Elkum, Naser; John, Sumi Elsa; Abufarha, Mohamed; Alsmadi, Osama; Thanaraj, Thangavel Alphonse.

In: Obesity, Vol. 25, No. 6, 01.06.2017, p. 1098-1108.

Research output: Contribution to journalArticle

Hebbar, P, Alkayal, F, Nizam, R, Melhem, M, Elkum, N, John, SE, Abufarha, M, Alsmadi, O & Thanaraj, TA 2017, 'The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related traits and mediates by interacting with Apo-A1', Obesity, vol. 25, no. 6, pp. 1098-1108. https://doi.org/10.1002/oby.21826
Hebbar, Prashantha ; Alkayal, Fadi ; Nizam, Rasheeba ; Melhem, Motasem ; Elkum, Naser ; John, Sumi Elsa ; Abufarha, Mohamed ; Alsmadi, Osama ; Thanaraj, Thangavel Alphonse. / The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity-related traits and mediates by interacting with Apo-A1. In: Obesity. 2017 ; Vol. 25, No. 6. pp. 1098-1108.
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abstract = "Objective: Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits. Methods: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome-wide association tests for obesity-related anthropometric traits were performed. Top associations were tested for replication in an independent cohort (1,176 unrelated Arabs). Resultant variants were investigated for interactions with obesity-related plasma biomarkers. Pathway analysis was performed on genes harboring markers in linkage disequilibrium (LD) with identified variants. Results: The rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist circumference (WC) at nearly genome-wide significance (P = 8.92E−08). WC was inversely related with Apo-A1 or high-density lipoprotein levels; individuals with the AG genotype exhibited stronger relationship than those with the reference AA genotype. Interaction involving the AG genotype (effect allele = G) significantly contributed to an increase in anthropometric traits (particularly WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped onto an interaction network (with TP53 as central element) of established obesity/diabetes-related protein components. Conclusions: The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.",
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AU - Alkayal, Fadi

AU - Nizam, Rasheeba

AU - Melhem, Motasem

AU - Elkum, Naser

AU - John, Sumi Elsa

AU - Abufarha, Mohamed

AU - Alsmadi, Osama

AU - Thanaraj, Thangavel Alphonse

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N2 - Objective: Despite alarming obesity levels in the Arabian Peninsula, its population lacks convincingly identified genetic determinants of obesity. A genome-wide association study was performed for obesity-related anthropometric traits in Arabs and to decipher mechanisms by which the variants mediate traits. Methods: The Illumina HumanOmniExpress BeadChip was used to genotype 1,353 Arab individuals (largely with Class I obesity) from Kuwait. Genome-wide association tests for obesity-related anthropometric traits were performed. Top associations were tested for replication in an independent cohort (1,176 unrelated Arabs). Resultant variants were investigated for interactions with obesity-related plasma biomarkers. Pathway analysis was performed on genes harboring markers in linkage disequilibrium (LD) with identified variants. Results: The rs9606756[c.67A>G,p.Ile23Val] variant from TCN2 was associated with waist circumference (WC) at nearly genome-wide significance (P = 8.92E−08). WC was inversely related with Apo-A1 or high-density lipoprotein levels; individuals with the AG genotype exhibited stronger relationship than those with the reference AA genotype. Interaction involving the AG genotype (effect allele = G) significantly contributed to an increase in anthropometric traits (particularly WC). Genes harboring single-nucleotide polymorphisms in LD with rs9606756 mapped onto an interaction network (with TP53 as central element) of established obesity/diabetes-related protein components. Conclusions: The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.

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