On the utilization of polygenic risk scores for therapeutic targeting.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Multifactorial Inheritance*; Precision Medicine/*methods; Depressive Disorder, Major/drug therapy ; Depressive Disorder, Major/genetics ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/genetics ; Female ; Humans ; Hypertension/drug therapy ; Hypertension/genetics ; Male ; Mutation ; Opioid-Related Disorders/genetics ; Opioid-Related Disorders/prevention & control ; Osteoporosis/genetics ; Osteoporosis/prevention & control ; Pharmacogenomic Testing/methods ; Preventive Medicine/methods ; Risk Factors

The promise of personalized genomic medicine is that knowledge of a person's gene sequences and activity will facilitate more appropriate medical interventions, particularly drug prescriptions, to reduce the burden of disease. Early successes in oncology and pediatrics have affirmed the power of positive diagnosis and are mostly based on detection of one or a few mutations that drive the specific pathology. However, genetically more complex diseases require the development of polygenic risk scores (PRSs) that have variable accuracy. The rarity of events often means that they have necessarily low precision: many called positives are actually not at risk, and only a fraction of cases are prevented by targeted therapy. In some situations, negative prediction may better define the population at low risk. Here, I review five conditions across a broad spectrum of chronic disease (opioid pain medication, hypertension, type 2 diabetes, major depression, and osteoporotic bone fracture), considering in each case how genetic prediction might be used to target drug prescription. This leads to a call for more research designed to evaluate genetic likelihood of response to therapy and a call for evaluation of PRS, not just in terms of sensitivity and specificity but also with respect to potential clinical efficacy.
Competing Interests: The author has declared that no competing interests exist.

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Date Created: 20190426 Date Completed: 20190508 Latest Revision: 20200225

20240105

PMC6483161

10.1371/journal.pgen.1008060

31022172