Research ArticleHuman Genetics

Aggregate penetrance of genomic variants for actionable disorders in European and African Americans

See allHide authors and affiliations

Science Translational Medicine  09 Nov 2016:
Vol. 8, Issue 364, pp. 364ra151
DOI: 10.1126/scitranslmed.aag2367

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

The problem of penetrance

It seems obvious that people who have mutations in genes known to cause disease in well-studied families would be more likely to also have the clinical features of disease if they were selected from the general population. But researchers have obtained mixed results on this point because of incomplete penetrance, i.e., not everyone who has a certain disease-causing mutation (a pathogenic variant) has the disease, raising questions about the value of genetic screening of people who are not sick. Natarajan and colleagues bring some clarity to this issue by examining two large groups of subjects—from the Framingham Heart Study and the African-American Jackson Heart Study—for the presence of mutations in 56 disease-related genes and for clinical features of their corresponding diseases. Even though the authors examined the genetic results of almost 5000 people, the number of these mutations was small. Nevertheless, these data clearly show that carrying a pathogenic variant markedly increases the chances of having the related disease.

View Full Text