Year: 2026
Type: article
Abstract: We leveraged allele frequencies from gnomAD, Regeneron Genetics Center Million Exome and Turkish Variome for 4591 disease genes from PanelApp and OMIM, and identified 97,135 pathogenic and 478,263 likely pathogenic variants using an American College of Medical Genetics and Genomics-based classifier. This expanded pathogenic and likely pathogenic variants nearly six-fold. On average, an individual is born with 4.70 pathogenic or likely pathogenic variants, of which 1.66 are compatible with a Mendelian condition at the genotype level; 1 in 11 has an actionable genotype, and 382 genes are candidates for carrier screening. A genome-first approach revealed the likelihood of having a genotype compatible with disease in 13 ICD-10 disease groups, for example, congenital (1 in 2.70), musculoskeletal/connective (1 in 3.00) and blood/immune (1 in 3.07 individuals). Evidence-based genetic epidemiology demonstrates the potential of personalized medicine for the implementation of early preventive measures and incentivization of lifestyle changes to enhance healthspan and lifespan.
Source: npj Genomic Medicine
Institutions: Bilkent University, Icahn School of Medicine at Mount Sinai, Koç University, Suna and İnan Kıraç Foundation, Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi, Hôpital Necker-Enfants Malades, Howard Hughes Medical Institute, Inserm, Université Paris Cité, Human Genetic of Infectious Diseases, Institut des Maladies Génétiques Imagine, Rockefeller University
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Howard Hughes Medical Institute, Fisher Center for Alzheimer's Research Foundation, St. Giles Foundation, Meyer Foundation, JPB Foundation, Rockefeller University, Fondation du Souffle, Georgia Clinical and Translational Science Alliance, Institut des maladies génétiques Imagine, Agence Nationale de la Recherche, Fondation Leducq, Fondation pour la Recherche Médicale, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, Türkiye Bilimler Akademisi, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1078920935, G112449207, G1418548345, G1942173203, G1979782309, G250961418, G282427092, G2862517037, G2939690567, G3458322075, G3958026571, G5485624415, G7240651115, G8670608220, G9000122699, G9000261049, Genome-Wide Dissection of Mendelian Susceptibility to Mycobacterial Disease, Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational Success
OpenAlex ID: W7130318025