With reference to the waist-to-hip ratio (WHR)—a particular measure of belly fat, or “central adiposity”—scientists have identified five new genes that merit closer scrutiny. Three of the genes are associated with increased WHR in both men and women, and the other two appear to affect WHR in women only.
One of the two genes that affect women only is called SHC1. This gene, which is highly expressed in fat tissue, appears to encode a protein that interacts with 17 other proteins known to have involvement in obesity. Perhaps most significantly, SHC1 was identified as a key hub in the medical subject headings (MESH)-defined obesity gene network, indicating its potential role in the regulation of metabolic and adipose pathways.
These results were published January 6 in Human Molecular Genetics, in an article entitled “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.” This article was produced by a research team led by Kira Taylor, Ph.D., an assistant professor at the University of Louisville School of Public Health and Information Sciences.
“This is the first time SHC1 has been associated with abdominal fat,” Dr. 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.”
Dr. Taylor’s team assessed the association between SNPs and BMI-adjusted waist circumference (WC) and WHR and unadjusted WC in up to 57,412 individuals of European descent from 22 cohorts collaborating with the National Heart, Lung, and Blood Institute’s Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20–80 years.
In the article, the authors wrote, “Study participants were genotyped using the ITMAT/Broad/CARe array, which includes about 50,000 cosmopolitan tagged SNPs across about 2,100 cardiovascular-related genes.” They also provided details of the fixed-effects meta-analysis that they carried out. “Functional analysis using ENCODE and eQTL databases revealed that several loci [associated with increased WHR] are in regulatory regions or regions with differential expression in adipose tissues.”
In addition, the authors noted that 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. They also cited evidence that SHC1 activates the insulin receptor, triggering multiple signaling events that affect fat cell growth. In their conclusions, the authors noted that as in previous studies, “the effect size and strength of the association is larger among females for most of the SNPs in comparison with males.”