The genetics of human obesity

Area of Science:

• Genetics
• Obesity Research
• Metabolic Disorders

Background:

• The heritability of obesity is well-established, prompting extensive genetic research over decades.
• Initial studies focused on rare monogenic/syndromic obesity, implicating hypothalamic leptin pathways in appetite regulation.
• Genome-wide association studies (GWAS) have identified common genetic variants associated with prevalent obesity across diverse populations.

Purpose of the Study:

• To review the genetic underpinnings of obesity, encompassing rare and common forms.
• To explore the concept of "missing heritability" in obesity and its contributing factors.
• To discuss the interplay between genetic predisposition and environmental influences on obesity.

Main Methods:

• Review of early genetic studies on rare obesity forms.
• Analysis of findings from genome-wide association studies (GWAS) for common obesity variants.
• Investigation into rare variants, copy number variations, and epigenetic modifications contributing to obesity heritability.

Main Results:

• Genetic factors, including rare and common variants, explain a significant portion of obesity heritability.
• Epigenetic changes and copy number variations also contribute to the genetic basis of obesity.
• The "missing heritability" is being elucidated through advanced genetic analyses.

Conclusions:

• A comprehensive understanding of obesity genetics involves rare variants, common variants, and epigenetic factors.
• The interaction between genetic susceptibility and environmental factors (diet, lifestyle) is crucial for obesity development.
• Advances in genetic research hold promise for developing targeted preventive and therapeutic strategies for obesity.