Independent of obesity itself, WHR is a key indicator of risk of diabetes, heart disease and mortality, and appears to be regulated differently in women and men.

Reykjavik, ICELAND, 11 October 2010 – In two of the largest metastudies of their kind to date, scientists from the GIANT consortium, including deCODE as well as hundreds of academic institutions on three continents, today report the discovery of eighteen new regions of the human genome contributing to obesity and thirteen new regions influencing waist-hip ratio (WHR). The studies bring together data on body mass index (BMI, a measure of obesity), WHR (a measure of body fat distribution), and detailed genotypic information, from more than a quarter of a million participants from Europe, North America and Australia. The findings demonstrate the effectiveness of collaborations such as GIANT for powering studies large enough to detect lower-impact genetic factors for common traits and diseases.

“To my mind, perhaps the most noteworthy aspect of these findings is that it has indeed been possible to find so many loci for WHR that are independent of BMI. Most of the BMI loci appear to affect central and neuronal processes regulating satiety and appetite. By contrast, the WHR loci appear to be involved in the development and distribution of adipose tissue. Thus, the genetics seems to be pointing us to biological distinctions between two components of the regulation of weight – how much we eat, and how and where calories are stored as fat. Also intriguing, many of the WHR loci show a significantly greater impact in women than in men, a distinction that is stronger here than in any other disease or trait we have looked at. From a health perspective, the distinctions drawn here between BMI and WHR are steps towards better understanding the role of these two traits as risk factors for a range of diseases,” said Kari Stefansson, deCODE CEO and a senior author on the BMI study.

The papers, “Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index,” and “Meta-analysis identifies 13 novel loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution,” are published online in Nature Genetics at www.nature.com/ng and will appear in an upcoming print edition of the journal.

deCODE scientists have discovered new genetic variants influencing BMI, weight and risk of obesity

As we all know to well, for decades the scales have been tipping in favor of obesity. The epidemic of obesity in many industrialized countries has been driven by many factors, including easy access to fast food, an increasingly sedentary lifestyle, insufficient daily physical activity. All of this while our genomes have evolved on a background of scarcity, often putting a premium on the ability of the body to turn food into fat and store energy for leaner times. A paper published today by deCODE scientists and academic colleagues from the US and Europe provide a significant advance in our knowledge of the underlying genetics and biology of obesity, providing new information for understanding and addressing obesity and perhaps nudging the scales the other way.
In a major study published today, the deCODE-led team reports the discovery of a large number of single-letter variations in the sequence of the human genome (SNPs) influencing body weight, body mass index (BMI) and risk of obesity. (BMI>30kg/m2). The discoveries were made be scanning over 300,000 SNPs in more than  30,000 individuals from Iceland, The Netherlands, and the United States, and then confirming the findings in individuals from Denmark and the multinational GIANT consortium, totaling close to 40,000 individuals. Interestingly, many of the variants discovered are located near genes related to energy sensing or food intake regulation in the brain, suggesting its importance in the development of obesity.   Although these variants only explain a small fraction of the variation in BMI, they provide new insght into the basic mechanisms underlying obesity and a first step towards identifying drug targets that can be used to address the global public health challenge of obesity.