André G. Uitterlinden
Laboratory for Population Genomics, Erasmus MC, Rotterdam, The Netherlands
a.g.uitterlinden [at] erasmusmc.nl
Abstract
Variance among individuals in disease susceptibility, treatment response and/or progression, is determined -in part- by genetic variation. Human genome sequencing has uncovered hundreds of millions of genetic variants, while DNA analysis technology has progressed to allow sequencing a human genome in <24hours, and to analyze millions of SNPs in millions of DNA samples using arrays.
Array technology has identified thousands of genetic factors for common disease by Genome Wide Association Studies (GWAS) in cohort studies and biobanks. Thousands of SNPs associated with disease risk for hundreds of diseases, have been combined in many disease-specific Polygenic Risk Scores (PRS). Some PRS are now evaluated in clinical trials to assess their added value in risk prediction, e.g. in population screening programs such as mammography for breast cancer. Interestingly, such PRS-es and clinically relevant DNA variants can be assessed using array genotyping (< 30 euro’s/sample).
World-wide large-scale sequencing projects are now ongoing, such as the European 1 million Genomes (1MG) Project, and stimulate national genome programs. The recently funded Genome of Europe (GoE) project will target to whole genome sequence (WGS) 100,000 citizens from 29 countries across Europe. Such WGS data will be made accessible for research and applications in care and prevention, such as comparison of particular DNA variations across ethnic groups and countries, specifying the population genetic structure of subgroups in the general population, and optimizing imputation capacity against improved genomic reference data.
Together, these developments have led to genetic information now entering the hospital clinic, whereby –in theory- all patients can be assessed by array genotyping for mutations, PRS, pharmacogenetics (PGx), and blood group/HLA typing for example, to help clinicians in decision making for diagnosis and treatment, and to provide self-empowerment for patients for prevention. Such a program, called GOALL (Genotyping On ALL patients) is currently running at Erasmus MC, The Netherlands. However, also outside of the (academic) hospital setting applications of using genetic information are explored, such as in population screening programs for breast or colon cancer. Aspects of these developments and outlooks to the future will be discussed.
Keywords: Genetic – Sequencing – Arrays – Genome – PRS