Genetics:
[1] & [2] Genes that influence obesity and body fat distribution
Embargoed until:
11-Feb-2015 13:00 US Eastern time | 18:00 London time
12-Feb-2015 03:00 Japanese time | 05:00 Australian Eastern time
DOI: 10.1038/nature14132
DOI: 10.1038/nature14177
Over 100 newly identified genetic signatures associated with obesity and fat
distribution in humans provide new insights into the factors that contribute to these
traits. The findings, reported in two studies in this week’s Nature, are based on the
analysis of genetic data for over half a million individuals, as part of the GIANT
research project, which aims to identify genes that regulate human body size and
shape. Obesity and fat accumulation predispose individuals to many diseases;
learning more about the genes and biological processes that influence these traits
will help to improve our understanding of their contribution to diseases and may
guide the development of weight-loss therapies.
Accumulation of fat, especially around the stomach, increases the risk of
cardiovascular and metabolic diseases. Karen Mohlke and colleagues examine the
genetic determinants of fat distribution and how these factors influence
cardiovascular and metabolic diseases in analyses of up to 224,459 individuals.
They identify 49 sites in the genome associated with waist-to-hip ratio — a
measure of body fat distribution — including 33 novel loci, and 19 additional
novel loci for other measures of waist and hip circumference. Some of the loci
display stronger effects in women than men, demonstrating that genetic regulation
of body fat distribution varies between the sexes. Analyses indicate that the loci
seem to contribute to variation in fat distribution by affecting processes involved in
fat cell development, blood vessel formation, gene expression and metabolic
regulation.
In a second study, Elizabeth Speliotes and colleagues investigate the genetic basis
of body mass index (BMI), a common measure of overall obesity, in up to 339,224
individuals. They find 97 genetic loci associated with BMI, of which 56 were
novel. The analyses indicate that the central nervous system has a role in obesity
susceptibility and highlight genes and biological processes that affect BMI,
including a pathway that responds to changes in feeding and fasting and that is
thought to be targeted by an FDA-approved weight-loss drug. This observation
supports the idea that identifying genes and pathways associated with obesity could
reveal new targets for weight-loss therapies.
CONTACT
Karen Mohlke (University of North Carolina, Chapel Hill, NC, USA) Author
paper [1]
Tel: +1 919 966 2913; E-mail: mohlke@med.unc.edu
Elizabeth Speliotes (University of Michigan, Ann Arbor, MI, USA) Author paper
[2]
Tel: +1 734 647 2964; E-mail: espeliot@med.umich.edu
Please link to the scientific papers in online versions of your report (the URLs will
go live after the embargo ends):
http://nature.com/articles/doi:10.1038/nature14132
http://nature.com/articles/doi:10.1038/nature14177