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.
authors.affiliation: Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon.
authors.forename: Michella
authors.initials: M
authors.lastname: Ghassibe-Sabbagh
authors.affiliation: Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon.
authors.forename: Marc
authors.initials: M
authors.lastname: Haber
authors.affiliation: Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon.
authors.forename: Angelique K
authors.initials: AK
authors.lastname: Salloum
authors.affiliation: Shafallah Medical Genetics Center, Doha, Qatar.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Al-Sarraj
authors.affiliation: Centre Hospitalier du Nord-CHN, Zgharta, Lebanon.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Akle
authors.affiliation: 1] Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon [2] University Medical Center - Rizk Hospital (UMC-RH), Lebanon.
authors.forename: Kamal
authors.initials: K
authors.lastname: Hirbli
authors.affiliation: Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon.
authors.forename: Jihane
authors.initials: J
authors.lastname: Romanos
authors.affiliation: Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon.
authors.forename: Francis
authors.initials: F
authors.lastname: Mouzaya
authors.affiliation: INSERM, UMRS872, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.affiliation: Bioinformatics and Pattern Discovery, IBM T. J. Watson Research Centre, Yorktown Hgts, NY 10598, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Platt
authors.affiliation: 1] Shafallah Medical Genetics Center, Doha, Qatar [2] University of Iowa Carver College of Medicine, Iowa City.
authors.forename: Hatem
authors.initials: H
authors.lastname: El-Shanti
authors.affiliation: 1] Lebanese American University, School of Medicine, Beirut 1102 2801, Lebanon [2] Harvard School of Public Health, Boston MA 02215, USA.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Zalloua
mesh_terms: D000368:Aged; D015897:Comorbidity; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007861:Lebanon / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D012359:tRNA Methyltransferases
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human