Background <p>β-Thalassemia major typically manifests between six months and two years of age. It is characterized by chronic anemia, and a range of multisystemic complications lead to increased morbidity and disease burden. It has a significant influence on patients’ mental and social health, making a biopsychosocial approach necessary for all encompassing therapy. This study examines how biopsychosocial, biochemical variables and genetic variants, namely the PDE7B gene SNP rs2327669, is associated with β-thalassemia major.</p> Methodology <p>Analysis of 400 patients and 400 controls, ages 2 to 18 years, was conducted with an emphasis on psychosocial aspects using a standardized questionnaire developed with the assistance of a psychiatrist and previously published studies to assess the psychological burden, biochemical indicators through biochemical analysis and genotyping with the help of Tetra ARMS-PCR.</p> Results <p>The findings presented here demonstrate the association between β-thalassemia major’s biopsychosocial, biochemical aspects and genetic predispositions. A significant association between the rs2327669 and clinical indicators, were found by SNP genotyping with significance value &lt; 0.05. In personality characteristics and SNP genotyping association it was found, neuroticism and introversion were associated to the GG mutant genotype, whereas conscientiousness and compassion were associated to the CC and CG genotype (<i>p-value &lt; 0.005</i>).</p> Conclusion <p>Through this study it was observed that, the PDE7B rs2327669 polymorphism is significantly associated with selected biochemical and psychosocial parameters in β-thalassemia major patients. Larger cohort studies are necessary in the future, so it could lead toward focused therapies that tackle physiological &amp; biopsychosocial issues, enhancing the clinical results and quality of life for β-thalassemia major patients.</p>