Color Makes Polygenic Scores Available to Participants Through New Study

Today, we are excited to announce our new Genetic Score Study, a research effort that makes genome-wide polygenic scores available to Color participants for the first time. These scores are a new kind of genetic analysis that integrate information from millions of changes in DNA into a single number to calculate an individual’s inherited risk for disease.

A polygenic score is based on DNA, which means that it does not change throughout an individual’s lifetime. Therefore, this genomic information can potentially identify people at high risk for common diseases such as coronary artery disease (CAD) before they develop any symptoms, which could enable early interventions to prevent disease.

At Color, our goal is to use genomic information to improve individual- and population-level health. To date, most genetic tests have focused on rare, monogenic mutations or variants that affect how an individual’s body may respond to certain medications. These mutations are usually a single misspelling in the DNA code and can lead to several-fold higher risk for disease. Some examples include mutations in the BRCA1 gene, which greatly increase an individual’s risk for breast cancer, or mutations in the LDLR gene, which can lead to early heart attacks.

Identifying carriers of rare, monogenic mutations can be hugely impactful for individuals and their families — in some cases providing an explanation for why they developed disease and in others providing an opportunity to seek expert care to prevent disease with targeted screening or therapy.

However, the genomics community has increasingly recognized that most individuals with common diseases such as CAD do not have a rare monogenic mutation. Rather, their inherited risk may be due to the cumulative effect of many variants scattered across the genome. Each of these alone has a very small contribution to heart disease risk — but in aggregate they can have a large effect.

Over the past year, we have worked closely with Drs. Sekar Kathiresan and Amit V. Khera to validate and launch our CAD Genetic Score Report. The CAD genetic score was first described in their landmark Nature Genetics paper in 2018, which suggested that up to 25 million people in the U.S. are at more than triple the normal risk for CAD.

One of the most interesting and new aspects of our CAD Genetic Score Report is the underlying technology we are using to perform it. Traditionally, most statistical genetics applications — assessing genetic ancestry and polygenic scores — have been calculated using genotyping arrays (also known as SNP chips). These arrays are relatively inexpensive to run, and they can look at several hundred thousand variants very quickly. But there is an important downside as well — because the SNPs on the array are fixed, you can only find what you’re already looking for. Since most of the existing commercial arrays are better-designed and optimized for those of European ancestry, scores calculated from array data may have an inherent bias in their applicability and performance across racial groups.

Color’s unique approach uses a new technology — called low-coverage whole genome sequencing (lcWGS) — to calculate polygenic scores. Instead of capturing the same pre-specified list of several hundred SNPs, we capture the entire genetic content of the genome at a low-depth in an unbiased way. By combining lcWGS with advanced computational tools to integrate information from each of the 6.6 million sites, we are able to accurately calculate the CAD genetic score. We tested and validated this new technique using samples from a diverse spectrum of genetic ancestry, confirming that the accuracy of polygenic scores at least as good as the traditional genotyping array approach and the ability to interpret the raw polygenic score within the context of individually-quantified genetic background. You can read more about how we did that in our pre-print, found here.

By launching Color’s Genetic Score Study, we will start to understand how individuals perceive and react to this new type of genetic score and add to the growing body of evidence demonstrating how it can be an important aspect of genome interpretation in the coming years. In addition, the data that we collect from the study will allow us to continue to improve the accuracy and performance of the score over time. Color’s Genetic Score Study is available for individuals who have gotten a Color Test in the last year with low coverage whole genome sequencing. Unlike Color’s clinical health reports, our genetic score reports are based on emerging science and are not intended for medical use or to diagnose any health conditions. Interested individuals can find out more at color.com.