How can polygenic inheritance be used in population screening for common diseases?

Genetics in Medicine

(2013)

15,

437–443

doi:10.1038/gim.2012.182

Received: 06 December 2012
Accepted: 07 December 2012
Published online: 14 February 2013

Abstract

Advances in genomics have near-term impact on diagnosis and management of monogenic disorders. For common complex diseases, the use of genomic information from multiple loci (polygenic model) is generally not useful for diagnosis and individual prediction. In principle, the polygenic model could be used along with other risk factors in stratified population screening to target interventions. For example, compared to age-based criterion for breast, colorectal, and prostate cancer screening, adding polygenic risk and family history holds promise for more efficient screening with earlier start and/or increased frequency of screening for segments of the population at higher absolute risk than an established screening threshold; and later start and/or decreased frequency of screening for segments of the population at lower risks. This approach, while promising, faces formidable challenges for building its evidence base and for its implementation in practice. Currently, it is unclear whether or not polygenic risk can contribute enough discrimination to make stratified screening worthwhile. Empirical data are lacking on population-based age-specific absolute risks combining genetic and non-genetic factors, on impact of polygenic risk genes on disease natural history, as well as information on comparative balance of benefits and harms of stratified interventions. Implementation challenges include difficulties in integration of this information in the current health-care system in the United States, the setting of appropriate risk thresholds, and ethical, legal, and social issues. In an era of direct-to-consumer availability of personal genomic information, the public health and health-care systems need to prepare for an evidence-based integration of this information into population screening.
Genet Med 2013:15(6):437–443

Keywords:

evidence-based medicine; genetics; genomics; polygenic model; public health; risk assessment; screening

In this issue of Genetics in Medicine, Chowdhury et al.¹ report on the recommendations of multidisciplinary expert workshops convened by the Foundation for Genomics and Population Health (PHG Foundation) in partnership with the University of Cambridge. Participants examined scientific, ethical, and logistical aspects of personalized population screening for prostate and breast cancer based on polygenic susceptibility. The authors recognized the promise of genetic stratification in population screening for breast and prostate cancer and identified key issues that need to be addressed before genetic stratification can be implemented in practice, the most important of which is the need to recognize the benefits and harms of stratified screening as compared with existing screening methods. They also identified several ethical issues such as discrimination of high-risk individuals and patient autonomy in relation to genetic testing of minors; the need for transparency and clear communication about genetic risk scores; and the need to develop new professional competencies and to assess cost effectiveness and acceptability of stratified screening programs before implementation.
We commend the authors for the thoughtful analysis and modeling of potential for improved effectiveness of screening and for early stakeholder engagement in a rapidly moving field. Here, we elaborate on the potential of population screening in an age of genomics and personalized medicine. At the outset, we acknowledge that although the promise of genomics will be first fulfilled in the diagnosis and management of monogenic disorders, its use in population screening for common complex diseases will lag behind due to significant evidentiary as well as implementation challenges.