• Rong Chen, Lisa Edelmann, Eric Schadt, et al. | Nature Biotechnology | 11 April 2016

    Investigating Resilience to Disease Through Population Genomics

    Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases

    Genetic studies of human disease have traditionally focused on the detection of disease-causing mutations in afflicted individuals. Here we described a complementary approach that seeks to identify healthy individuals resilient to highly penetrant forms of genetic childhood disorders. To accomplish this, we carried out the largest genomics study carried out at the time, analyzing over 589,000 genomes in search of individuals harboring highly penetrant, deleterious mutations in their DNA that should have caused catastrophic illness in childhood, but these individuals never manifested clinical disease and thus are protected.The protecting mechanism, if uncovered, offers a direct therapeutic path for disease. In our search we identified 13 individuals resilient to severe Mendelian childhood diseases, including diseases such as cystic fibrosis, where we identified individuals harboring the most damaging cystic fibrosis mutations, but never having manifested disease into their 40’s and 50’s.