MOAMEN ABDELFADIL ISMAIL,ALI QASEM ABDULLAH ALABDULSALAM, OMAR ABDULLAH MOHAMMED ABUBAKR-ALMULLA,FATIMAH MOHAMMED AL- OMAIR, JUMANAH HABIB ALIBRAHIM, HAWRA WASEL JASIM ALQATIFI,WALAA ALI ALMUSALLAM,HASSAN YOUSEF ALDHNEEN,HUSSAIN YOUSEF BOHASSAN,10--GHADAH ABDULLAH ALZIYADI, MOHAMMED AHMED SAEED ALSHAKHS,RAWAN FAISAL ALAHMED,REEM FAHD MOUTI AL-MUGHTHAWI
DOI: https://doi.org/Background: Genetic and familial factors are recognized contributors to Type II Diabetes Mellitus (T2D), yet their comparative and clinical significance remain underexplored in relation to traditional risk factors such as obesity and sedentary behavior.
Objective: To evaluate the contribution of genetic predisposition and family history to the risk of developing T2D through a systematic review of empirical evidence published between 2010 and 2024.
Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, Web of Science, Embase, and Google Scholar using terms related to T2D, genetics, and family history. Eligible studies included adult populations, reported on genetic/familial exposures, and used observational or experimental designs. Risk of bias was assessed using the Newcastle-Ottawa Scale, AXIS tool, and RoB 2.0, depending on study type.
Results: A total of 27 studies were included. Family history was associated with a 2–5-fold increase in T2D risk, independent of known genetic variants. GWAS identified over 400 susceptibility loci, yet common variants explained only 5–15% of heritability. Polygenic risk scores improved risk stratification but remained insufficient alone. Obesity and lifestyle factors interacted with genetic predisposition, often modifying the absolute risk. Gene–environment interactions were especially pronounced in early-onset and high-BMI populations.
Conclusions: Family history remains a more powerful predictor of T2D than polygenic models alone. Future research should focus on enhancing predictive models using multi-ancestry data and integrating genetics into personalized care strategies. Prevention remains highly feasible even among genetically predisposed individuals, particularly through targeted lifestyle interventions.
