A fascinating new paper by Johnston et al., just published in the American Journal of Human Genetics, has given us considerable insight into the prevalence of rare genetic disorders in the healthy, adult population of the USA.
Based on their analysis of exome data from 951 apparently healthy participants in the ClinSeq study cohort, Johnston et al. have shown that about 3% of this group of 45- to 65-year-old individuals had a mutation linked to some form of genetically identifiable disorder (even though they may have had no clinically significant indications of disease).
Earlier studies had given estimates of the prevalence of such genetic conditions in the healthy adult population as being < 0.02%. Clearly this was a major under-estimate. We already knew that the prevalence of clinically evident rare diseases (genetic and non-genetic in etiology) in the entire US population is of the order of 25 to 30 million people (about 9 or 10% of the entire population). What are the clinical implications of this new finding? That's still to be determined. And it may take a while. Bear in mind that many of us are going to be carriers of genetic mutations that are rare and that, while these mutations may be associated with risk for certain rare disorders, they are not necessarily going to cause such disorders on their own. On the other hand, the population tested in the ClinSeq study cohort excludes all the children and others who are either born with identifiable genetic disorders (because of newborn screening programs or well-known family risk) or have genetic disorders that are liable to become evident in the first 30 or so years of life.
There is a brief non-scientific report on the findings of this study in The Washington Post.
What is clear from this study is that risk for a rare disorder among healthy 45- to 65-year-olds is about 100 times higher than we had thought in the past!