A genome-first approach to aggregating rare genetic variants in LMNA for association with electronic health record phenotypes.
Joseph ParkMichael G LevinChristopher M HaggertyDustin N HartzelRenae JudyRachel L KemberNosheen Rezanull nullMarylyn D RitchieAnjali T OwensScott M DamrauerDaniel James RaderPublished in: Genetics in medicine : official journal of the American College of Medical Genetics (2019)
Pathogenic LMNA variants are an underdiagnosed cause of cardiomyopathy. We also find that LMNA loss of function may be a primary cause of renal disease. Finally, we show the value of aggregating rare, annotated variants into a gene burden and using PheWAS to identify novel ontologies for pleiotropic human genes.