Technological readiness and implementation of genomic-driven precision medicine for complex diseases.

Maria F Gomez ,J Gustav Smith ,Sara Hägg ,Patrick F Sullivan ,Ai Catrina ,Christina Jern ,Catarina Almqvist ,Claes Ohlsson ,Beatrice Melin ,Hannes Hagström ,Kamila Czene ,Johan Sundström ,Richard Rosenquist ,Dirk Repsilber ,Bo Jacobsson ,Per Hall ,Åsa Johansson ,Mikaela Friedman ,Mikael Benson ,Gunnel Nordmark ,Mia Wadelius ,Anders Mälarstig ,Jonas Halfvarson ,Ingrid Kockum ,Paul W Franks ,Kristina Johnell ,Matej Orešič ,Lars Klareskog ,Marju Orho‐Melander ,Tove Fall ,Sarah E Bergen ,Erik Melén ,Lars Rönnblom

doi:10.1111/joim.13330

Abstract

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

Highlights

The resolution, throughput and cost of genome sequencing are such that we can routinely apply these technologies at scale
In the past two decades, genetic testing has become increasingly widespread in patients with a familial predisposition to certain diseases
This review summarizes the views of clinicians and scientists who specialize in genomic-driven precision medicine (GDPM) of complex diseases within the framework of Genomic Medicine Sweden (GMS)

Summary

Introduction

The resolution, throughput and cost of genome sequencing are such that we can routinely apply these technologies at scale. This presents unprecedented opportunities for medical practice and studies of disease aetiology. The application of genomics to the field of medicine to improve diagnosis, prevention, treatment and prognosis – genomic-driven precision medicine (GDPM) – has been widely discussed [1,2,3,4,5,6] and is becoming standard of care, for cancer, rare diseases and adverse drug reactions. Mutations in BRCA1 or BRCA2 indicate a high risk for breast and ovarian cancer and a mutation in HTT causes Huntington’s disease. Focus is being placed on expanding GDPM beyond cancers

Background

Conclusions

Findings

Conflict of interests