A new study published at the weekend reports the findings of a large scale genetic study that identifies 13 new genes associated with body fat distribution, seven of which appear to have stronger effects in women than in men.

Corresponding author Dr Cecilia Lindgren, of the Wellcome Trust Centre for Human Genetics at Oxford University in the UK, and her co-authors are members of an international consortium comprising 400 scientists from 280 research institutions worldwide; their paper appears in the 10 October online issue of Nature Genetics.

We already know from previous studies that fat stored in the abdomen (the “apple” shape) increases the risk of type 2 diabetes and heart disease, even after adjusting for obesity, whereas fat stored in the hips, thighs and buttocks (the “pear” shape) may actually protect against these diseases.

Thus waist-to-hip ratio (WHR), a measure of body fat distribution, is now well-established as a risk factor in these diseases, independently of body mass index (BMI), a measure of obesity that compares weight to height.

However while there is evidence that WHR can run in families, until this study, little was known about the genes involved.

For their investigation, Lindgren and colleagues conducted a meta-analysis of large-scale genome-wide association studies (GWAS) to find gene variants that might be strongly linked to WHR. (A meta-analysis is a way of pooling results from several studies and treating them statistically as if they came from one large study.)

They pooled data on 77,000 participants from 32 studies and checked their results against data from another 29 studies covering over 113,500 participants. The data showed 14 gene regions were linked to waist-to-hip ratio, confirming one that had already been discovered, but revealing 13 that had not been linked to this measure of body fat distribution before.

The 13 new regions were at the following locations (loci): RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4.

The already known one that they confirmed was at: LYPLAL1.

The regions they discovered include known genes that help control levels of cholesterol, triglycerides, insulin and insulin resistance, and they hope their identification will improve understanding of why deposits of fat in some parts of the body are more closely linked to metabolic disorders than to obesity.

While only explaining about 1 per cent of the variation in waist-to-hip ratio, the researchers said the discovery could help researchers find important biological pathways that control where and how our bodies deposit fat.

They also found that seven of the 13 regions appeared to have stronger links with waist-to-hip ratio in women than in men, potentially explaining why women’s bodies deposit fat differently to men’s.

Lindgren told the press that:

“By finding genes that have an important role in influencing fat distribution and the ways in which that differs between men and women, we hope to home in on the crucial underlying biological processes.”

“Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.”
Iris M Heid, Anne U Jackson, Joshua C Randall, Thomas W Winkler, Lu Qi, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, M Carola Zillikens, et al.
Nature Genetics, Published online: 10 October 2010

Source: Massachusetts General Hospital.

Written by: Catharine Paddock, PhD