A new collaborative study identifies rare mutations and disease causing genetic variants through the linkage of sequencing data from participants and their electronic health records.

The DiscovEHR study, a collaboration between the Regeneron Genetics Centre and Geisinger Health System, is the largest of its kind so far.

By sequencing the exome (the part of the genome that codes for proteins) of 50,762 participants, and using patients’ de-identified electronic health records (EHRs) provided by Geisinger to match clinically documented phenotype data with sequencing data, researchers found over four million single nucleotide variants, insertions and deletions. Of these, 176,000 were predicted to cause a partial or complete loss of gene function. By linking the rare variants with clinical phenotypes documented in participant’s EHRs, the team was able to better understand the consequences of this presumed loss of function. The researchers estimated that 3.5% of the participants had one or more mutations associated with one of 76 clinically-actionable diseases.

A more detailed look at participants with three genes known to contribute to Familial Hypercholesterolemia which causes abnormally high cholesterol levels and potentially severe early heart disease – found that of the 229 participants with the known variants, only 58% were currently receiving treatment, and less than 50% were taking the correct dosage.

David J Carey, co-author describes the research as "an important step forward for precision medicine", one that other precision medicine efforts might wish to consider using as a blueprint.