Obesity Kills: Can Genetics Help in the Targeting of Obesity Prevention?

Abstract

• Obesity is becoming a worldwide epidemic and is a major public-health-threatening problem in most countries in the world. A recent paper in The Lancet [1] involving 19.2 million participants broke the news by forecasting that, if the current trends of weight gain continue, by 2025, the global obesity (BMI>30) prevalence will reach 18% among men and surpass 21% among women (39% for all); severe obesity will exceed 6% among men and 9% among women (BMI>35, 15% for all).• Obesity means an excess accumulation of body fat tissue and is caused by a combination of excessive food intake, a lack of physical activity, and genetic susceptibility.• Severe and morbid obesity are associated with highly elevated risks of adverse health outcomes, i.e., metabolic diseases (type 2 diabetes), higher morbidity and mortality for a variety of diseases as well as higher overall mortality. It has been estimated that overweight decreases an individual's life expectancy by eight years.• The number of gene loci associated significantly (p<5 × 10 -8 ) in genome-wide analyses (GWA) with adult weigh traits, i.e., body mass index, waist-to-hip ratio and body fat % -is currently over 110 [2][3][4] and 60 loci were recently found to associate with birth weight [5], which is a predictor of adulthood obesity. The identified new loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses provide strong support for a role of the central nervous system, the neurosecretory system, in susceptibility to obesity and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis. The ongoing genome sequencing efforts will soon widen the genetic map of weigh-trait and obesity-related gene loci. This provides stronger genetic instruments for the prediction of obesity and allows the scientists to construct obesity risk calculators considering lifestyle, clinical measures, family history, ethnicity and individual genome variation information in the estimation of the life-time risk of obesity.• At the moment, we do not have sufficient means to stop this "fat epidemic" or prevent its consequences, but we also know that existing morbid obesity and its consequences are extremely difficult to treat.In recent work by Dr. Horikoshi and members of the Early Growth Genetics (EGG) Consortium in Nature [5], the researchers analysed genetic differences throughout the genomes of nearly 154,000 people from across the world. By relating the genetic profiles of these individuals to information on birth weight, the researchers were able to identify 60 regions of the genome that were driving the differences in birth weight. They then analysed data from previous GWA studies on conditions including body weight, body mass index, obesity in adulthood, childhood obesity, blood pressure, diabetes and heart disease, and found that many of the same genomic regions were highly significantly associated with...