February 11, 2015

expert reaction to two studies on genes, obesity and fat distribution

Two papers published in the journal Nature have reported the importance of several regions in the human genome as being important in the distribution of fat in the body, as well as for obesity. These include genes involved in metabolism and the nervous system, and the researchers suggest that these might be useful in the future as a focus for targeting disease.

Dr Nicholas Timpson, Reader in Genetic Epidemiology, University of Bristol, said:

“There is no question that body composition is correlated with a swathe of downstream health factors. Analyses which are able to assert causality have also shown evidence suggesting that the same measures are likely to be important in determining adverse health events. Until recently and outside the realm of syndromic forms of disorder, there had been little success in the analyses of the genetic underpinning of this important collection of anthropometric traits. Technological advances in the mid-2000s revolutionised this situation and the analysis of common genetic variation across the entire genome saw the first findings around genetic contributions to BMI explicitly. From this, two key lessons were firstly that the architecture of the genetic contribution is complex and multifactorial and secondly very large studies of anthropometry and genome wide genetic data are required to help to understand these contributions further.

“The two papers published today simultaneously widen the physical measurement base for investigation of body composition, increase the size of the investigation into body composition genetics and make great use of available, genetic epidemiological resources. Consequently, the understanding of the contribution of common genetic variation to BMI (directly) and body composition has increased markedly. In the case of BMI, analyses in up to 339,224 individuals has taken the list of confirmed genes and advanced it with 56 new and independent genetic signals. Five of these genetic regions demonstrate clear evidence of multiple association signals in one place and many loci have effects on other related biological phenomena. In terms of the size of the contributions, together the existing and new genetic variants account for 2.7% of BMI variation and new estimates of the total contribution of our genes suggest that common variation accounts for ~20% of BMI variation.

“This work does not hold a complete answer to variation in body composition, nor does it complete the genetic investigation of these traits. However the traits being investigated are extremely relevant to population health, they are theoretically modifiable at the level of policy and future intervention and the novel and exciting findings will advance understanding in the field considerably.”

‘New genetic loci link adipose and insulin biology to body fat distribution’ by Shungin et al. and ‘Genetic studies of body mass index yield new insights for obesity biology’ by Locke et al. published in Nature on Wednesday 11 February 2015. 

Declared interests

None declared