Clinical Utility of Genetic Testing in Obesity: A Case-Based Review in the Context of Type 2 Diabetes

Background: Obesity has a significant genetic component, accounting for up to an estimated 70% of individual susceptibility. Advances in genome-wide association studies (GWASs) and next-generation sequencing (NGS) have enhanced identification and characterization of genetic forms of obesity, facilitating more precise and individualized treatment approaches. The phenotypic heterogenicity of the disease of obesity, along with the limited predictive value of clinical features, hinders the accurate identification of genetic forms of the disease. Therefore, genetic testing represents a critical diagnostic modality to confirm etiology and inform precision-based therapeutic strategies. Aim: To compare the clinical utility, interpretation and potential impact of direct-to-consumer (DTC-GT) and clinician-directed genetic testing for obesity in the context of type 2 diabetes. Methods: This case-based review evaluated a patient with severe obesity and type 2 diabetes who underwent both DTC-GT and clinician-directed genetic testing for obesity. A structured literature review using PubMed, Scopus, Web of Science, and Google was undertaken to identify the resources of both testing approaches. Tables and a schematic figure were developed to summarize the findings. Results: Neither testing approach identified clinically actionable obesity-associated genetic variants or a monogenic cause of obesity. However, the DTC-GT report concluded that the patient was at “high risk” of obesity and was provided to the patient without a referral to genetic counseling which contributed to patient misunderstanding. Conclusions: This case, interpreted alongside the reviewed literature, suggests that clinician-directed genetic testing may better support reliable interpretation of obesity-associated genetic findings and disease management than DTC-GT. Larger studies are warranted to confirm these observations.