Integrated polygenic risk score can more accurately identify people at high risk of developing coronary artery disease across diverse ancestries over a commonly used clinical tool.
March 16, 2023, Menlo Park, CA. MyOme, Inc., a clinical whole genome platform analysis company and a leader in the development of polygenic risk scores with relevance across multiple ancestries, will share data from three presentations at the 2023 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting being held March 14-18, 2023. Featured as one of only 20 “Rapid Fire” presentationsis the development and validation of an integrated polygenic risk score that improved coronary artery disease prediction.
Most tests and tools that assess risk for coronary artery disease (CAD), the leading global cause of death, have been validated on a narrow population. The most commonly used tool, the Atherosclerotic Cardiovascular Disease (ASCVD) risk estimator or Pooled Cohort Equation (PCE), includes traditional measures like cholesterol and is used to predict 10-year risk of CAD and guide statin treatment initiation decisions. Polygenic risk scores (PRS), the aggregation of millions of genetic variants of small effect size into a single score, have the potential to improve the accuracy of clinical risk tools. To support diverse ancestries, MyOme developed and validated an integrated risk score (IRS) that combines a cross-ancestry PRS (caPRS) with ASCVD-PCE.
In the study that included participants of diverse ancestry, key findings include:
- IRS model outperformed the baseline ASCVD-PCE model across all population groups with largest improvements in South Asian and European ancestry groups
- IRS model identified an additional 12.42% individuals at high risk of CAD among those classified as borderline/intermediate risk by the ASCVD-PCE model
“IRS demonstrated that CAD risk prediction is more accurate when clinical risk prediction tools are integrated with PRS,” said Kate Im, PhD, head of research of MyOme. ”Improvements in risk accuracy using Myome’s multiethnic approach were shown to be particularly effective in individuals of South Asian ancestry — noteworthy since CAD mortality is approximately twice as high in South Asians as compared to Europeans. By better identifying high-risk individuals, IRS identifies those who may benefit from early intervention such as a statin.“
In addition to the IRS, MyOme’s work in long-read technology development for clinical applications will also be highlighted at the meeting.
Thursday, March 16 from 10:30 AM – 12:00 PM MT
Rapid Fire Presentation Thursday, March 16 12:45 PM – 1:15 PM MT
Abstract P333: Polygenic risk scores improve 10-year risk prediction of coronary artery disease in individuals at borderline and intermediate clinical risk
Additional research presented on MyOme’s whole genome platform:
Thursday, March 16 from 10:30 AM – 12:00 PM MT
Abstract P659: Whole-genome sequencing as a first assay has the potential to shorten diagnosis time for neurodevelopmental disorders
In a study to assess the ability of whole genome sequencing (WGS) to replace chromosomal microarray (CMA) and exome testing for diagnosis of neurodevelopmental disorders, WGS was able to identify 100% of 106 large (≥50kb) copy number variants (CNVs) previously identified by CMA. WGS had high recall and precision for single nucleotide variants (SNVs) and was able to identify biallelic variants in multiple cases. Whole-genome sequencing can provide a more comprehensive genetic analysis on large CNVs, SNVs, and gene-level CNVs to replace CMA and whole-exome sequencing for patients with neurodevelopmental disorders.
Friday, March 17 from 10:30 AM – 12:00 PM MT
Abstract P498: Development and validation of a clinical nanopore sequencing assay to confirm microdeletions and microduplications
In a study to validate the Oxford Nanopore Technologies (ONT) long-read technology as a clinical assay, 100% of CNVs (n=55) initially detected using short-read genome sequencing were confirmed with ONT long-read technology. Targeted ONT long-read sequencing can reliably confirm copy number variants in a clinical test and has the potential to improve the rate of clinical diagnosis of rare disease.
MyOme is a clinical whole genome analysis platform company helping families understand their risk for inherited diseases. As a leader in polygenic modeling, MyOme leverages the power of the whole genome for a lifetime of actionable insights. Certified under the Clinical Laboratory Improvement Amendments (CLIA), MyOme is based in Menlo Park, California. For more information, please visit myome.com.