"JAMA" "Personal Genome Testing" Industry Alarm: Most "pathogenic" genetic variants have low risk of disease

To address this need, researchers at the Icahn School of Medicine at Mount Sinai analyzed DNA sequence and electronic health record data from thousands of individuals stored in two large biobanks

"A major goal of this research is to generate useful high-level statistics to quantitatively assess the likely impact of known disease-causing genetic variants on an individual's risk for disease

Over the past 20 years, scientists have identified hundreds of thousands of genetic variants that can lead to various diseases

In the study, the researchers addressed this question by searching large-scale DNA sequencing data from 72,434 individuals to find 37,780 known variants, and then scanning each individual's health records for corresponding disease diagnoses

Preliminary results showed that 157 diseases in their dataset were potentially associated with 5,360 variants that were either defined as "pathogenic" by the widely cited, NIH-supported public library ClinVar, or predicted by bioinformatics algorithms as "functional".

"At first, I was very surprised by the results

Despite these results, the risks associated with certain genetic variants remain high

Further findings showed additional advantages of utilizing biobank data

The team also found that the presence of certain variants may depend on an individual's ethnicity, and identified more than 100 variants that were found exclusively in individuals of non-European ancestry

Finally, the authors list several possible ways in which the study itself may underestimate or overestimate risk

"While more research needs to be done, we think this study is a good first step in ultimately providing physicians and patients with the accurate and subtle information they need to make more precise diagnoses," Dr Do said

Iain S.