Not only Size Matters: Genetic Megastudies Draw out Distinctions between Obesity and Waist-Hip Ratio
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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, 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.
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.
