Scientists have identified 12 new genes that are somewhat strange bedfellows: Some link gallstones and blood cholesterol levels, others link melatonin and sleep patterns to small increases in glucose levels and larger jumps in the risk of diabetes.
While these associations are surprising, all the genes are potential new drug targets and some of them could help explain conditions that have been a mystery.
The 12 new genes relate to cholesterol and glucose levels, but several point to somewhat unexpected links between these traits and other conditions, says Goncalo Abecasis, associate professor of biostatistics at the School of Public Health (SPH) who co-directed the cholesterol study. Cristen Willer, a postdoctoral researcher working with Michael Boehnke, a professor at SPH, was lead analyst and joint first author of the study along with Sekar Kathiresan of Massachusetts General Hospital and Harvard Medical School.
Cholesterol is a strong predictor of heart disease and in a previous study Abecasis, Boehnke, Willer and colleagues had shown that genetic variants that raise LDL cholesterol (low density lipoprotein or so-called bad cholesterol) levels also increase the risk of heart disease. The current study describes the most detailed assessment of the genetics of cholesterol to date, examining genetic variants and cholesterol levels in more than 40,000 individuals.
“An important finding is that several of these genes have multiple different changes that can affect cholesterol,” Willer says.
“We think looking at this list of genes in individuals with extremely high cholesterol may clarify a lot of those unexplained cases,” Abecasis says.
In the cholesterol study, U-M scientists and collaborators at more than 10 institutions in the United States and Europe located 30 genetic variants associated with cholesterol levels, including 11 new ones. Notably, several of the newly implicated genetic variants also were related to the risk of gallstones and certain rare forms of diabetes.
“Each of these genes is a potentially interesting drug target,” Abecasis says. Statins, a class of cholesterol lowering drugs used to reduce the risk of heart disease, target the HMGCR gene, one of the genes identified in the study. The other genes in the study could lead to entirely new and more effective therapies to manage cholesterol levels and reduce the risk of heart disease.
In the paper studying glucose levels, Abecasis and Boehnke collaborated with researchers across the globe to discover genetic changes strongly associated with a small increase in glucose levels in non-diabetic individuals.
The gene, called the melatonin receptor, helps regulate the circadian clock, among other things. The finding strengthens the association between disrupted sleep patterns and diabetes, Boehnke says.
Two papers explaining the findings appear online in Nature Genetics in advance of the January print edition.
