Anne Tybjærg-Hansen is Chief Physician at the Department of Clinical Biochemistry, Section for Molecular Genetics, at Rigshospitalet, Copenhagen University Hospital, Copenhagen, as well as Professor of Clinical Biochemistry with Focus on Translational Molecular Cardiology at the University of Copenhagen, Copenhagen, Denmark. After completing her medical degree at the University of Copenhagen, she undertook additional studies at the University of Copenhagen and the Lipid Clinic at Righospitalet, Hagedorn Research Laboratory, Gentofte, Denmark, and the British Heart Foundation’s Molecular Biology Research Group, London, UK. Professor Tybjaerg-Hansen has made major contributions to the understanding of the genetics of lipoproteins and their association with atherosclerotic cardiovascular disease. She is a member of the steering committees of the Copenhagen City Heart Study and the Copenhagen General Population Study, and a member of the European Atherosclerosis Consensus Panel, contributing to statements on familial hypercholesterolaemia, hypertriglyceridaemia, triglyceride-rich lipoproteins and high-density lipoprotein, and lipoprotein(a). Professor Tybjaerg-Hansen was the recipient of the Anitschkow Award presented by the European Atherosclerosis Society in 2018.
Monday 01 June 09:00
Can polygenic scores reach clinical practice?
Advances in genomic research, biobank resources and computational methodologies offer the tantalising prospect of personalised genomic medicine to facilitate more appropriate medical interventions to reduce the burden of disease. Recent efforts have been directed to investigating the clinical utility of polygenic risk profiling to identify groups of individuals who could benefit from the knowledge of their likely susceptibility to disease.
The polygenic risk score is based on the premise that multiple gene variants with weak associations with disease risk collectively may enhance disease predictive value in the population. Information from the increasing number of biobanks has been instrumental in the development of very large longitudinal cohorts that are needed to verify and test polygenic risk scores. Translation to the clinic, however, poses several challenges. Consideration of the contribution of the genetic component to the underlying mechanisms of the disease is critical, as are appropriate selection of variants for use in the risk score and their weighting. Importantly, the disparity in precision between those of European descent and other ethnicities, a direct consequence of Eurocentric biases in genome-wide association studies, highlights an urgent need for greater diversity in genetic studies. Integration of the use of polygenic risk profiling with other tools and metrics for disease diagnosis and prognosis is also critical.
Benn M, Tybjærg-Hansen A, Nordestgaard BG. Low LDL cholesterol by PCSK9 variation reduces cardiovascular mortality. J Am Coll Cardiol 2019;73:3102-14.
Marott SCW, Nordestgaard BG, Tybjærg-Hansen A, Benn M. Causal associations in type 2 diabetes development. J Clin Endocrinol Metab 2019;104:1313-24.
Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort. Eur Heart J 2019. doi: 10.1093/eurheartj/ehz402.