Synonymous Mutations Show Neutrality in Human Disease
Researchers at the University of Oxford and UK Biobank have found that synonymous mutations are predominantly neutral when it comes to causing human disease - suggesting they may not be the primary cause of certain conditions after all.
Dec. 24, 2022 8:13AM
Generated in 17.0 seconds
A picture of a DNA strand with a magnifying glass over it, highlighting one specific gene or mutation.
A recent high-profile paper claimed that synonymous mutations could be just as important as nonsynonymous ones in causing human disease. However, a new @AJHGNews Commentary by researchers at the University of Oxford and UK Biobank has found that synonymous mutations are predominantly neutral when it comes to causing human disease. Using sequence data from 500K @uk_biobank exomes, the researchers showed that synonymous mutations are under less selective pressure than missense variants and PTVs, even when considering synonymous variants that reduce codon optimality. They also showed that there is a far greater enrichment of missense- and PTV-driven associations with the 5,000 phenotypes assessed in their UK Biobank PheWAS (https://t.co/F71kZXqVK6 and https://t.co/YB9bNtplCK). The findings suggest that while some synonymous mutations may be involved in human diseases, they are generally not the primary cause of such conditions. This could have implications for genetic testing and medical treatments for certain diseases going forward.