Genetic causes of obesity: mapping a path forward

Area of Science:

• Genetics
• Obesity Research
• Pharmacology

Background:

• Significant progress in understanding the genetic causes of obesity over the past 30 years.
• Obesity is a complex, heterogeneous disease requiring research beyond traditional metrics like body mass index (BMI).

Purpose of the Study:

• To highlight the accelerating pace of genetic discovery in obesity.
• To emphasize the potential of new findings for identifying biological mechanisms and drug targets.
• To underscore the value of polygenic scores (PGSs) for early obesity risk prediction and prevention.

Main Methods:

• Leveraging genetic variant catalogs for variant-to-function (V2F) translation.
• Focusing gene discovery on refined adiposity traits beyond BMI.
• Developing and improving polygenic scores (PGSs) for obesity risk prediction.

Main Results:

• Identification of additional genetic loci associated with obesity.
• Uncovering novel biological mechanisms underlying obesity.
• Advancement in the predictive power of polygenic scores (PGSs).

Conclusions:

• Obesity genetics research is at an unprecedented level, offering new avenues for therapeutic development.
• Refined genetic insights and improved polygenic scores (PGSs) hold significant potential for early intervention and personalized prevention strategies.
• The convergence of obesity genetics and weight-loss medication research promises new drug targets.