NIH Study Supports Genomic Approach to Addressing Genetic Conditions

Looking at more than a dozen genotype-first studies, researchers funded by the NIH categorized several benefits of using a genotype-first approach when treating genetic diseases.

“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” commented Caralynn Wilczewski, PhD, a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core and first author of the paper.

In the NIH study, researchers shared three discoveries from the genotype-first methodology. In one example, they found that a genetic abnormality in the TPSAB1 gene was associated with clinical traits, including symptoms linked with connective tissues, the nervous system, and the gastrointestinal tract. Additionally, the study uncovered novel symptoms associated with previously undiscovered disorders. The methodology also allowed researchers to identify the function of several genomic variants, which could help clinicians understand novel diseases.

“Genomics has the potential to change reactive medicine into preventative medicine,” said Leslie Biesecker, MD, NIH distinguished investigator, director of NHGRI’s Center for Precision Health Research, and a senior author of the article. “Studying how taking a genotype-first approach to research can help us learn how to model predictive and precision medicine in the future.”

Genotype-first assessments use genomic assays to identify populations of patients with specific genomic variants. Clinicians then study that population’s phenotype or expressed characteristics, creating a better understanding of the traits and symptoms associated with particular genes.

The genotype-first approach differs from typical treatments, where clinicians and researchers first identify patients experiencing symptoms and then look for variants to explain their findings. This phenotype-first approach limits researchers by confining their understanding of symptoms to specific genes and shrinking the scope of their study.

To conduct their research, collaborators at the NHGRI relied on genomic data sharing hosted by programs like ClinSeq and the National Institute of Allergy and Infectious Disease Centralized Sequencing Protocol. Using both resources, the team analyzed 16,000 participants who had undergone genomic sequencing in the past.

Genetic data is of utmost importance to clinicians, researchers, and healthcare professionals looking to build a better practice of genomics.  The primary vector for improving genetic data sets involves more robust genetic testing that enhances the quality of available information and allows for productive research. Another part of the equation focuses on advancing genomic interfaces and the interoperability of genetic data to support researchers in collecting information for genomic applications. Using this new genomic data, researchers expect to eventually accelerate their creation of precision medicines for hard-to-treat diseases.