Plenary 2 Tuesday 01 June – Session 1

From genetic discovery to clinical interventions to combat atherosclerosis: Mark Daly, Helsinki, Finland

Future CVD management: from gene to phenotype to treatment

Mark Daly is Director of the Institute for Molecular Medicine Finland (FIMM) since February 2018, in addition to affiliations with Harvard Medical School, Massachusetts General Hospital and the Broad Institute, and co-director of the Program in Medical and Population Genetics. He received his B.Sc. in physics from the Massachusetts Institute of Technology and his Ph.D. in human genetics from Leiden University, the Netherlands. He received the Curt Stern Award from the American Society of Human Genetics in 2014, was elected to the National Academy of Medicine in 2017, and was awarded Aarhus University’s Honorary Doctorate at the Faculty of Health in 2019. His research primarily focuses on the development and application of statistical methods for the discovery and interpretation of genetic variation responsible for complex human disease. His laboratory has made major contributions to gene discovery in inflammatory bowel disease, autism and schizophrenia. He is a co-architect of the FinnGen project, a landmark public-private effort to integrate decades of medical registry data with genomic data in 10% of the Finnish population, and coordinates the leadership team of the COVID-19 Host Genetics Initiative (HGI) (https://www.covid19hg.org).

Predicting disease risk is integral to preventative medicine and clinical management. Typically this takes account of both nonmodifiable factors, such as age, sex and family history of disease, as well as modifiable risk factors including lifestyle. In recent years, there has been interest in the use of genetic information to aid risk prediction, made possible by advances in genomic tools and techniques. Genome-wide association studies have shown that complex diseases such as atherosclerosis have a polygenic basis that influences predisposition. These variants can be combined into a polygenic risk score to evaluate an individual’s susceptibility to disease.

The translation of genetics to the development of polygenic risk scores has been shown to improve prediction of susceptibility to disease, such as for early-onset coronary heart disease as demonstrated in studies using FinnGen biobank data. Beyond this role in risk prediction, genetics may also provide a practical strategy for improving population health, allowing targeted intervention against modifiable risk factors in individuals at increased susceptibility to impact the disease trajectory.  Translation of polygenic risk information for screening or for guiding lifestyle and therapy needs to address key challenges, including the paucity of information in individuals of non-European ancestry. Beyond this, there is also the need for studies investigating the implementation and health-economic value of application of polygenic risk information in both population health and clinical settings.

Recent references

Mars N, Koskela JT, Ripatti P, Kiiskinen TTJ, Havulinna AS, Lindbohm JV, Ahola-Olli A, Kurki M, Karjalainen J, Palta P, FinnGen Project, Neale BM, Daly M, Salomaa V, Palotie A, Widén E, Ripatti S. Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers. Nature Med 2020; 26:549-57.

Covid 19 Host Genetics Initiative, Ganna A, Daly M. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet 2020;28:715-8.

Tanigawa Y, Wainberg M, Karjalainen J, Kiiskinen T, Venkataraman G, Lemmelä S, Turunen JA, Graham RR, Havulinna AS, Perola M, Palotie A, FinnGen Project, Daly MJ, Riva MA. Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma. PLoS Genetics 2020;16(5):20.

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