New genes present drug targets for managing cholesterol and gluc...( ANN ARBOR Mich.---Scientists have ide...)

ANN ARBOR, Mich.---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. Nature Genetics will publish two papers explaining the findings online Dec 7, in advance of the January print edition.

The 12 new genes relate to cholesterol and glucose levels, but several point to somewhat surprising links between these traits and other conditions, said Goncalo Abecasis, associate professor of biostatistics at the University of Michigan School of Public Health who co-directed the cholesterol study. Cristen Willer, a postdoctoral researcher working with Michael Boehnke, a professor at the U-M 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 said. For example, in the PCSK9 gene there are common variants that affect about 40 percent of the population and increase LDL by about 3-6 milligrams per deciliter, a fairly small amount. Another variant affects roughly 2 percent of individuals but increases LDL by about 15-
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