Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity

Area of Science:

• Genetics
• Endocrinology
• Metabolic Diseases

Background:

• Genetic factors play a significant role in obesity development.
• Advances in sequencing technologies have accelerated the identification of genetic contributors to obesity.
• There is growing recognition of the prevalence of monogenic obesity.

Purpose of the Study:

• To review and aggregate information on monogenic obesity over the past five years.
• To provide guidance for genetic testing in clinical practice.
• To highlight the role of genetic variants in obesity etiology and management.

Main Methods:

• Literature review of studies published in the last five years.
• Analysis of genetic variants associated with monogenic obesity.
• Synthesis of current knowledge on genetic testing and therapeutic strategies.

Main Results:

• Identification of novel genes and variants contributing to monogenic obesity, primarily in the leptin-melanocortin pathway.
• Recognition that while individual genetic mutations are rare, collectively genetic etiologies for obesity are not uncommon.
• Evidence of common variants influencing lifelong weight gain tendencies or offering protection against monogenic obesity.
• Some genetic obesity conditions are responsive to targeted treatments, with ongoing research into new therapies.

Conclusions:

• Genetic testing is increasingly utilized in clinical care for obesity, driven by technological advances and new treatments.
• Monogenic obesity, though individually rare, represents a significant collective cause of severe, early-onset obesity.
• Targeted therapeutic strategies based on genetic risk are an emerging and promising frontier in obesity management.