Discovery of seven new sites in the human genome found to influence obesity

Dec 14 2008

In one of the largest studies of its kind, a multinational team led by scientists from deCODE genetics has reported the discovery of common variations at seven new sites in the human genome found to influence obesity.

The study analyzed more than 300,000 single-letter variations (SNPs) across the genome of more than 30,000 people from Iceland, the Netherlands, and the United States, and confirmed the findings in data from more than 40,000 individuals from Denmark and the US-based GIANT Consortium. deCODE is incorporating the novel SNPs on chromosomes 1, 2, 3, 6, 11, 12 and 19 reported today in its deCODEme(TM) personal genome analysis service, and subscribers will receive an update to their personal profiles. The paper, entitled "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity," is published today in the online edition of Nature Genetics at http://www.nature.com/ng, and will appear in an upcoming print edition of the journal.

"This study essentially doubles in one fell swoop the number of known and replicated genetic factors contributing to obesity as a public health problem. And what we are seeing in obesity are a large number of common genetic risk factors with a relatively modest impact on disease. One of the most notable aspects of these discoveries is that most of these new risk factors are near genes that regulate processes in the brain. This suggests that as we work to develop better means of combating obesity, including using these discoveries as the first step in developing new drugs, we need to focus on the regulation of appetite at least as much as on the metabolic factors of how the body uses and stores energy," said Kari Stefansson, CEO of deCODE and senior author on the paper.

"Today's findings also underscore our ability to employ our population-based resources and statistical knowhow in Iceland as a cornerstone of large-scale multinational collaborations to identify and replicate the inherited causes of the most complex phenotypes. These new variants may point to valuable new drug targets, and we are already integrating them into deCODEme.(TM) We look forward to expanding upon our productive collaboration with colleagues in the US and Europe to continue to increase our understanding of the biology that underlies obesity," Dr. Stefansson added.

Obesity results from the consumption of more calories than the body uses, and it represents a growing public health problem worldwide, particularly in industrialized countries. Obesity is a major risk factor for diseases such as type 2 diabetes, a range of cardiovascular conditions, and even some forms of cancer. One third of the population of the United States is now classified as obese, and the World Health Organization (WHO) estimates that around the world as many as 400 million people are obese.

Obesity is a quintessentially complex condition. Behavioral factors such as diet, eating habits and lack of exercise play a major role, but these interact with genetic factors that influence the regulation of appetite as well as how the body uses energy and stores it as fat. The aim of the study published today was to identify more of these genetic factors as a means of better understanding the biological processes that contribute to obesity. This information can be used to inform efforts to develop better means of combatting it. The discovery phase of the study published today correlated more than 300,000 SNPs with data on weight and body mass index (BMI). BMI is a measure used to relate weight to height, calculated as an individual's weight in kilograms divided by their height in meters squared, and individuals with a BMI greater than 30 are defined as obese. The 43 SNPs identified in this first scan were then analyzed in 5,500 Danes and genotypic data from the 33,000 participants in the GIANT Consortium's research. This analysis yielded SNPs linked to overweight and obesity at seven regions of the genome not previously known to be involved in obesity; identified new SNPs at previously known obesity-linked sites in the genome; and confirmed and refined the impact on obesity of previously published SNPs at four other sites in the genome.

deCODE and the authors would like to thank the participants in this study, and to acknowledge the fruitful collaboration with the GIANT Consortium, which included data from this study in its own meta-analysis also published today. The research performed at deCODE was partly funded through the European Community's ENGAGE project, grant agreement HEALTH-F4-2007-201413. Support for the US research was provided by the US National Institutes of Health, and for the Danish research by the Lundbeck Foundation Centre of Applied Medical Genomics and the Danish Health Research Council.

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