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The genetics of adiposity.

Ruth Jf Loos1

  • 1The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Current Opinion in Genetics & Development
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Genetic studies have found over 500 loci linked to obesity. Alternative methods focusing on diverse populations and specific genetic variants identified new obesity-related genes, potentially aiding weight loss drug development.

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Area of Science:

  • Genetics and Genomics
  • Obesity Research
  • Metabolic Diseases

Background:

  • Genome-wide association studies (GWAS) have identified over 500 genetic loci associated with adiposity traits.
  • Most discoveries stem from large-scale meta-analyses of body mass index (BMI) and waist-to-hip ratio (WHR) in European ancestry populations.
  • Previous efforts have limitations in capturing novel loci through alternative approaches.

Purpose of the Study:

  • To explore novel genetic loci associated with adiposity traits using alternative discovery approaches.
  • To investigate the role of non-European ancestry populations, refined adiposity measures, and low-frequency coding variants.
  • To identify potential pharmacological targets for weight loss interventions.

Main Methods:

  • Utilized genome-wide discovery efforts beyond traditional large-scale meta-analyses.
  • Focused on non-European ancestry populations to increase genetic diversity.
  • Incorporated refined adiposity measures and analysis of low-frequency coding variants (MAF < 5%).

Main Results:

  • Identified additional novel genetic loci associated with adiposity that were not found in previous studies.
  • Loci linked to overall obesity implicate central nervous system pathways.
  • Loci associated with fat distribution highlight pathways involved in adipocyte biology.

Conclusions:

  • Alternative approaches significantly expand the discovery of obesity-related genetic loci.
  • Understanding causal genes within identified loci is crucial for biological insights.
  • Newly identified genes represent potential targets for future weight loss pharmacotherapies.