From monogenic to polygenic obesity: recent advances

Area of Science:

• Genetics
• Endocrinology
• Obesity Research

Background:

• Obesity exhibits high heritability, with both rare monogenic forms and common polygenic factors contributing to body weight regulation.
• Molecular genetic studies have identified key genes and pathways involved in obesity, enhancing our understanding of body weight control.

Purpose of the Study:

• To review the genetic underpinnings of obesity, from monogenic forms to polygenic influences.
• To highlight the impact of genetic discoveries on understanding obesity and developing therapeutic strategies.

Main Methods:

• Review of molecular genetic studies, including family and animal studies.
• Analysis of genome-wide association studies (GWAS) and meta-analyses to identify polygenic variants.
• Examination of specific gene variants, such as those in the FTO gene.

Main Results:

• Monogenic obesity forms, like leptin deficiency, have been identified, leading to targeted therapies.
• Common variants, particularly in the FTO gene, contribute to elevated BMI, with effects accumulating across multiple variants.
• As of December 2009, 17 independent genomic regions with confirmed polygenic variants influencing obesity were identified.

Conclusions:

• Genetic research has significantly advanced the understanding of obesity's complex etiology.
• Further identification of genetic variants is expected to explain more of obesity's heritability.
• Anticipation of novel diagnostic, treatment, and prevention strategies for obesity based on genetic insights.