Researchers supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, announced the publication of a groundbreaking TOPMed study which analyzed more than 53,000 whole genomes, primarily from minority populations.
The study, which appears in the February 10 online issue of the journal Nature, examines one of the largest and most diverse data sets of high-quality whole genome sequencing—a person’s complete set of DNA. The genetic data could shed new light on how heart, lung, blood, and sleep disorders impact people with diverse racial and ethnic backgrounds, who often are underrepresented in genetic studies.
The whole genomes used in the study are based on data from participants in the NHLBI’s Trans-Omics for Precision Medicine Program (TOPMed). Researchers there hope this data will one-day lead to treatments tailor-made to individual patients, as well as shed light on racial and ethnic health disparities. Among its many findings, the current study:
- Identified 400 million genetic variants, more than 78% of which had not been described before
- Produced the best quality genotype data available for people with African ancestry, who showed the highest genetic variability of the groups studied
- Provided new insights into certain gene variants that adversely affect the metabolism of prescription drugs and whose biological effects may vary by race and ethnic group
The Trans-Omics for Precision Medicine (TOPMed) program seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci.
Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation.
Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.
Genomic Medicine Meeting
On February 9-10, 2021, the National Human Genome Research Institute (NHGRI) will sponsor its 13th Genomic Medicine meeting, Genomic Medicine XIII: Developing a Clinical Genomic Informatics Research Agenda.
The objectives of this meeting are to:
- Define the current status of genomic-based clinical informatics resources and related knowledge gaps;
- Determine facilitators and barriers that affect the development and deployment of genomic-based clinical informatics resources and research needed to address them;
- Identify research needed to improve how genomic-based clinical informatics resources impact the patient and clinician decision-making processes.
The main goal of this meeting is to develop a research strategy on the use of genomic-based clinical informatics resources to improve the detection, treatment and reporting of genetic disorders in clinical settings.