Genome-wide study of Europeans finds new genetic risk factors for 'bad' cholesterol
A genome-wide study of thousands of individuals throughout Europe has identified 22 genetic regions (loci) that affect lipid levels, a common indicator of cardiovascular disease. Six of these loci are newly discovered and may contribute to the accuracy of genetic profiles, which could be used to screen for individuals at risk for metabolic disorders or dyslipidemia. The findings, published in the journal Nature Genetics, also showed genetic differences in lipid metabolism between men and women. The international team of researchers examined serum lipid data from between 17,798 and 22,562 Europeans (depending on the lipid trait studied). Theirs was a genome-wide association analysis of 16 European studies, in which data from large groups of subjects were combined in order to identify genetic factors affecting serum levels of high- and low-density lipoprotein cholesterol, triglycerides and total cholesterol. Data were provided by the ENGAGE ('European network for genetic and genomic epidemiology') project, which integrates very large-scale genetic data from a substantial number of large European sample sets. ENGAGE, financed with EUR 12 million from the EU under the Seventh Framework Programme (FP7), aims to translate the wealth of data produced by large-scale research efforts into information of direct relevance to future advances in clinical medicine. 'Serum lipids are important determinants of cardiovascular disease and are related to morbidity,' the study explains. It has been established that circulating lipid levels are to some extent inherited, and studies have shown that numerous genes are involved in lipid metabolism. Although previous studies looking at individuals with type 2 diabetes found 19 loci that control serum lipid levels, this did not go far enough in helping to predict cardiovascular disease. In the current study, the population studied did not have any specific disease, making it the first to find lipid-gene links by looking at the general population. The team discovered six lipid-associated loci, two of which include genes that encode proteins known to be involved in lipid metabolism. Doctors commonly look at classical risk factors such as age, sex and weight when evaluating whether a patient is at risk for cardiovascular disease or metabolic disorders. But prediction of such disorders could be significantly improved with the help of a genetic screening tool. The researchers looked at whether their new knowledge could improve 'genetic risk profiles', which might enable early preventive strategies such as treatment with statins - a class of drugs used to lower cholesterol levels - and diet control. They noted that using the genetic data their ability to predict total cholesterol was improved; this has important implications for predicting high levels of 'bad' cholesterol (hypercholesterolemia) or coronary heart disease. Additionally, the researchers wanted to see whether these differences could be confirmed by looking at the genetic loci associated with lipids, as it is well known that lipid values for men and women differ. 'None of the published GWA [genome-wide analysis] studies have addressed the potential sex-based difference in genetic risk profiles for lipids,' the study reads. 'Here we found significantly different sex-specific effects for some genes, as expected from epidemiological and clinical data.' 'We can be confident that the increased understanding of the control of lipid levels that will come from these genetic discoveries, will, in time, lead to improved ways of treating and preventing heart disease and stroke,' said Professor Mark McCarthy of the University of Oxford in the UK. 'In addition, as we become better at identifying those individuals who are most at risk of these diseases, we should be able to target our therapeutic and preventative efforts more efficiently, perhaps focusing on changing lifestyles in those most likely to benefit.' New tools to study many thousands of DNA samples in a short time have made large-scale genome analysis possible. 'Since 2007, human genetics has achieved results that would have been unimaginable only five years ago,' explained Professor Leena Peltonen of the Wellcome Trust Sanger Institute in the UK. 'But this is merely the dawn of new understanding. New, more powerful studies, such as our work on lipid levels, will illuminate the areas and the variants of our genome that play an important part in human disease.'