Plenge Lab
Date posted: August 28, 2018 | Author: | No Comments »

Categories: Embedded Genomics Human Genetics Precision Medicine

[I am an employee of Celgene. All views expressed here are my own.]

What is the clinical significance of residing within the tail of a distribution for disease risk? A new study published in Nature Genetics uses a composite polygenic score to measure extremes of genetic risk(see original article here). The authors make the bold statement: “it is time to contemplate the inclusion of polygenic risk prediction in clinical care”. In this blog, I briefly review the paper, frame the impact of the study in terms of “long tails”, and propose how genetic tails may be used as part of a healthcare system reimagined.

The premise of the paper is that a genome-wide polygenic score (GPS) – a composite genetic test that includes thousands and sometimes millions of genetic variants – can identify a small number of individuals from the general population that have an elevated risk.  The study applies polygenic risk scores to five common diseases but spends most attention to coronary artery disease (CAD). For each disease, the increase in risk is approximately 3- to 5-fold higher among individuals at the extreme of the polygenic tail compared to those in the general population – see Figure 2a (and below) for CAD, where ~8% of the general population is at a 3-fold increase in risk based on a polygenic risk score.…

Read full article...