European genetic variants associated with type 2 diabetes in North African Arabs

Abstract

Recent genome-wide association studies (GWAS) and previous approaches have identified many genetic variants associated with type 2 diabetes (T2D) in populations of European descent, but their contribution in Arab populations from North Africa is unknown. Our study aimed to validate these markers and to assess their combined effects, using large case-control studies of Moroccan and Tunisian individuals. Overall, 44 polymorphisms, located at 37 validated European loci, were first analyzed in 1055 normoglycaemic controls and 1193 T2D cases from Morocco. Associations and trends were then assessed in 942 normoglycaemic controls and 1446 T2D cases from Tunisia. Finally, their ability to discriminate cases from controls was evaluated. Carrying a genetic variant in BCL11A, ADAMTS9, IGF2BP2, WFS1, CDKAL1, TP53INP1, CDKN2A/B, TCF7L2, KCNQ1, HNF1A, FTO, MC4R and GCK increased the risk of T2D when assessing the Moroccan and Tunisian samples together. Each additional risk allele increased the susceptibility for developing the disease by 12% (P = 9.0 × 10(-9)). Genotype information for 13 polymorphisms slightly improved the classification of North Africans with and without T2D, as assessed by clinical parameters, with an increase in the area under the receiver operating characteristic curve from 0.64 to 0.67 (P = 0.004). In addition to TCF7L2, 12 additional loci were found to be shared between Europeans and North African Arabs. As for Europeans, the reliability of genetic testing based on these markers to determine the risk for T2D is low. More genome-wide studies, including next-generation sequencing, in North African populations are needed to identify the genetic variants responsible for ethnic disparities in T2D susceptibility.