Excess abdominal fat is an indicator for heart disease, type 2 diabetes and cancer and a person's measure of such belly fat is reflected in the ratio of waist circumference to hip circumference.

Some estimate that genetics account for a broad range, 30 to 60 percent, of this waist-to-hip ratio (WHR).

Kira Taylor, Ph.D., M.S., assistant professor in the University of Louisville School of Public Health and Information Sciences, and colleagues have listed five new genes they say are associated with increased WHR. They did an analysis of more than 57,000 people of European descent and searched for genes that increase risk of high waist-to-hip ratio, independent of overall obesity. They investigated over 50,000 genetic variants in 2,000 genes thought to be involved in cardiovascular or metabolic traits. 

Their analysis identified three new genes associated with increased WHR in both men and women, and discovered two new genes that appear to affect WHR in women only. Of the latter, one gene, SHC1, appears to interact with 17 other proteins known to have involvement in obesity, and is highly expressed in fat tissue. In addition, the genetic variant the team discovered in SHC1 is linked to another variant that causes an amino acid change in the protein, possibly changing the function or expression of the protein.

"This is the first time SHC1 has been associated with abdominal fat," Taylor said. "We believe this discovery holds great opportunity for medicinal chemistry and eventually, personalized medicine. If scientists can find a way to fine-tune the expression of this gene, we could potentially reduce the risk of excessive fat in the mid-section and its consequences, such as cardiovascular disease."

Prior research has found that mice lacking the SHC1 protein are leaner, suggesting this molecule may have a role in metabolic imbalance and premature cell deterioration by supplying too much nutrition for normal growth and development.

Additional evidence finds SHC1 activates the insulin receptor, triggering multiple signaling events that affect fat cell growth.

Citation: Sachiko Yoneyama, Yiran Guo, Matthew B. Lanktree, Michael R. Barnes, Clara C. Elbers, Konrad J Karczewski, Sandosh Padmanabhan, Florianne Bauer, Jens Baumert, Amber Beitelshees, Gerald S. Berenson, Jolanda M.A. Boer, Gregory Burke, Brian Cade, Wei Chen, Rhonda M. Cooper-Dehoff, Tom R. Gaunt, Christian Gieger, Yan Gong, Mathias Gorski, Nancy Heard-Costa, Toby Johnson, Michael J. Lamonte, Caitrin Mcdonough, Keri L. Monda, N. Charlotte Onland-Moret, Christopher P. Nelson, Jeffrey R. O'Connell, Jose Ordovas, Inga Peter, Annette Peters, Jonathan Shaffer, Haiqinq Shen, Erin Smith, Liz Speilotes, Fridtjof Thomas, Barbara Thorand, W. M. Monique Verschuren, Sonia S. Anand, Anna Dominiczak, Karina W. Davidson, Robert A. Hegele, Iris Heid, Marten H. Hofker, Gordon S. Huggins, Thomas Illig, Julie A. Johnson, Susan Kirkland, the Look AHEAD Research Group, Wolfgang König, Taimour Y. Langaee, Jeanne Mccaffery, Olle Melander, Braxton D. Mitchell, Patricia Munroe, Sarah S. Murray, George Papanicolaou, Susan Redline, Muredach Reilly, Nilesh J. Samani, Nicholas J. Schork, Yvonne T. Van Der Schouw, Daichi Shimbo, Alan R. Shuldiner, Martin D. Tobin, Cisca Wijmenga, Salim Yusuf, the GIANT Consortium, the CARe IBC Consortium, Hakon Hakonarson, Leslie A. Lange, Ellen W Demerath, Caroline S. Fox, Kari E North, Alex P. Reiner, Brendan Keating, and Kira C. Taylor, 
'Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations, Hum. Mol. Genet. January 4 2014 doi:10.1093/hmg/ddt626. Source: University of Louisville