T2DM GWAS in the Lebanese population confirms the role of TCF7L2 and CDKAL1 in disease susceptibility

Michella Ghassibe-Sabbagh; Marc Haber; Angelique K. Salloum; Yasser Al-Sarraj; Yasmine Akle; Kamal Hirbli; Jihane Romanos; Francis Mouzaya; Dominique Gauguier; Daniel E. Platt; Hatem El-Shanti; Pierre A. Zalloua

doi:10.1038/srep07351

T2DM GWAS in the Lebanese population confirms the role of TCF7L2 and CDKAL1 in disease susceptibility

Michella Ghassibe-Sabbagh, Marc Haber, Angelique K. Salloum, Yasser Al-Sarraj, Yasmine Akle, Kamal Hirbli, Jihane Romanos, Francis Mouzaya, Dominique Gauguier, Daniel E. Platt, Hatem El-Shanti, Pierre A. Zalloua^*

^*Corresponding author for this work

Cancer and Genomic Sciences

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Abstract

Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are crucial to the understanding of Type 2 Diabetes Mellitus (T2DM) pathophysiology. We report a GWAS on the genetic basis of T2DM in a 3,286 Lebanese participants. More than 5,000,000 SNPs were directly genotyped or imputed using the 1000 Genomes Project reference panels. We identify genome-wide significant variants in two loci CDKAL1 and TCF7L2, independent of sex, age and BMI, with leading variants rs7766070 (OR = 1.39, P = 4.77 × 10^-9) and rs34872471 (OR = 1.35, P = 1.01 × 10^-8) respectively. The current study is the first GWAS to find genomic regions implicated in T2DM in the Lebanese population. The results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populations and provide a plausible component for understanding molecular mechanisms involved in the disease.

Original language	English
Article number	7351
Number of pages	9
Journal	Scientific Reports
Volume	4
DOIs	https://doi.org/10.1038/srep07351
Publication status	Published - 8 Dec 2014

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https://doi.org/10.1038/srep07351Licence: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND)

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title = "T2DM GWAS in the Lebanese population confirms the role of TCF7L2 and CDKAL1 in disease susceptibility",

abstract = "Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are crucial to the understanding of Type 2 Diabetes Mellitus (T2DM) pathophysiology. We report a GWAS on the genetic basis of T2DM in a 3,286 Lebanese participants. More than 5,000,000 SNPs were directly genotyped or imputed using the 1000 Genomes Project reference panels. We identify genome-wide significant variants in two loci CDKAL1 and TCF7L2, independent of sex, age and BMI, with leading variants rs7766070 (OR = 1.39, P = 4.77 × 10-9) and rs34872471 (OR = 1.35, P = 1.01 × 10-8) respectively. The current study is the first GWAS to find genomic regions implicated in T2DM in the Lebanese population. The results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populations and provide a plausible component for understanding molecular mechanisms involved in the disease.",

author = "Michella Ghassibe-Sabbagh and Marc Haber and Salloum, {Angelique K.} and Yasser Al-Sarraj and Yasmine Akle and Kamal Hirbli and Jihane Romanos and Francis Mouzaya and Dominique Gauguier and Platt, {Daniel E.} and Hatem El-Shanti and Zalloua, {Pierre A.}",

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AU - Ghassibe-Sabbagh, Michella

AU - Haber, Marc

AU - Salloum, Angelique K.

AU - Al-Sarraj, Yasser

AU - Akle, Yasmine

AU - Hirbli, Kamal

AU - Romanos, Jihane

AU - Mouzaya, Francis

AU - Gauguier, Dominique

AU - Platt, Daniel E.

AU - El-Shanti, Hatem

AU - Zalloua, Pierre A.

PY - 2014/12/8

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N2 - Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are crucial to the understanding of Type 2 Diabetes Mellitus (T2DM) pathophysiology. We report a GWAS on the genetic basis of T2DM in a 3,286 Lebanese participants. More than 5,000,000 SNPs were directly genotyped or imputed using the 1000 Genomes Project reference panels. We identify genome-wide significant variants in two loci CDKAL1 and TCF7L2, independent of sex, age and BMI, with leading variants rs7766070 (OR = 1.39, P = 4.77 × 10-9) and rs34872471 (OR = 1.35, P = 1.01 × 10-8) respectively. The current study is the first GWAS to find genomic regions implicated in T2DM in the Lebanese population. The results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populations and provide a plausible component for understanding molecular mechanisms involved in the disease.

AB - Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are crucial to the understanding of Type 2 Diabetes Mellitus (T2DM) pathophysiology. We report a GWAS on the genetic basis of T2DM in a 3,286 Lebanese participants. More than 5,000,000 SNPs were directly genotyped or imputed using the 1000 Genomes Project reference panels. We identify genome-wide significant variants in two loci CDKAL1 and TCF7L2, independent of sex, age and BMI, with leading variants rs7766070 (OR = 1.39, P = 4.77 × 10-9) and rs34872471 (OR = 1.35, P = 1.01 × 10-8) respectively. The current study is the first GWAS to find genomic regions implicated in T2DM in the Lebanese population. The results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populations and provide a plausible component for understanding molecular mechanisms involved in the disease.

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T2DM GWAS in the Lebanese population confirms the role of TCF7L2 and CDKAL1 in disease susceptibility

Abstract

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