CDKAL1 rs7756992 polymorphism and the risk of type 2 diabetes among Moroccans: A systematic review and meta-analysis.

Abstract

The CDKAL1 rs7756992 polymorphism is an established type 2 diabetes mellitus (T2DM) susceptibility locus; however, its role in the Moroccan population remains poorly characterized. This study provides the first rigorous meta-analysis of this variant in Morocco, following the PRISMA guidelines (PROSPERO: CRD42024549118). We systematically searched five databases until October 2024 and identified 10 studies that investigated 86 single nucleotide polymorphisms (SNPs) across 50 genes in the Moroccan population. Only CDKAL1 rs7756992 met the criteria for meta-analysis: ≥3 independent studies with Hardy-Weinberg equilibrium (HWE) in the control group (P≥0.05). Using R (version 4.2.1), we examined six genetic models and pooled odds ratios using random-effects models (REML, Hartung-Knapp adjustment). Heterogeneity was assessed using I2 statistics, and publication bias using funnel plots and trim-and-fill analysis. Three studies (n=3685: 1963 cases and 1722 controls) met the inclusion criteria with HWE satisfaction (all P≥0.05). The allelic model (G vs. A) demonstrated a significant association (OR=1.11, 95% CI: 1.02-1.21, 95% PI: 0.67-1.86, P=0.02) with no detectable heterogeneity (I2=0%, P=0.85). The homozygote comparison showed the strongest effect (GG vs. AA: OR=1.21, 95% CI: 1.13-1.30, P<0.001). Prediction intervals (95% PI: 0.67-1.86) were 6.3-fold wider than confidence intervals, reflecting τ2 estimation uncertainty when k is small rather than genuine between-study heterogeneity (I2=0%). This meta-analysis identified CDKAL1 rs7756992 as a modest T2DM susceptibility locus in the Moroccan population, with effect sizes consistent with global estimates. However, the small number of studies (k=3) necessitates replication in larger independent cohorts (n>5000) to refine effect estimates and establish population-specific genetic architecture.