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The genetics of human obesity

  • Jill Waalen
    Correspondence
    Reprint requests: Jill Waalen, The Scripps Research Institute and the Scripps Translational Science Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037
    Affiliations
    The Scripps Research Institute and the Scripps Translational Science Institute, La Jolla, California
    Search for articles by this author
      The heritability of obesity has long been appreciated and the genetics of obesity has been the focus of intensive study for decades. Early studies elucidating genetic factors involved in rare monogenic and syndromic forms of extreme obesity focused attention on dysfunction of hypothalamic leptin–related pathways in the control of food intake as a major contributor. Subsequent genome-wide association studies of common genetic variants identified novel loci that are involved in more common forms of obesity across populations of diverse ethnicities and ages. The subsequent search for factors contributing to the heritability of obesity not explained by these 2 approaches (“missing heritability”) has revealed additional rare variants, copy number variants, and epigenetic changes that contribute. Although clinical applications of these findings have been limited to date, the increasing understanding of the interplay of these genetic factors with environmental conditions, such as the increased availability of high calorie foods and decreased energy expenditure of sedentary lifestyles, promises to accelerate the translation of genetic findings into more successful preventive and therapeutic interventions.

      Abbreviations:

      BMI (Body mass index), CNV (Copy number variants), CPG (cytosine-phosphate-guanine), GCTA (Genome-wide complex trait analysis), GWAS (Genome-wide association study), ITMAT (Institute for Translational Medicine and Therapeutics), MAF (Minor allele frequency), PPARG (peroxisome proliferator-activated receptor gamma), SNP (Single-nucleotide polymorphism), WC (waist circumference), WHR (waist-to-hip ratio)
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