"The GWAS are genetic epidemiology studies often involving tens of thousands of patients and controls, originally designed to link isolated DNA locus to the risk of developing complex common disorders, such as atherosclerosis", says Dr Bj?śrkegren. "These studies now need to be complemented with clinical studies where the patients also are screened for intermediate molecular phenotypes in disease-relevant organs. The computational capacities and expertise required to address simultaneously all molecular activities and their relative risk-enrichment are available, all that remains is to start recruiting this kind of cohorts."

The findings suggest that the severity of atherosclerosis depends on the rate of the migration of white blood cells from the blood into the atherosclerotic plaques. Although this pathway is already known to play a role in atherosclerosis, the Swedish findings suggest that it is the rate limiting step for disease progression. However, Dr Bj?śrkegren admits that the exact roles of all 128 genes in atherogenesis remain unexplained. Future studies will focus on understanding the details of how these genes actually contribute to atherosclerosis in cell cultures and animal model systems.

Source: PLoS Genetics

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