biostudies-literatureBerger SINIDDK NIH HHSNCRR NIH HHSNIGMS NIH HHSra30https://www.ebi.ac.uk/biostudies/studies/S-EPMC3068558biostudies-literatureUnknown3(118)Long QT syndrome (LQTS) is a congenital or drug-induced change in electrical activity of the heart that can lead to fatal arrhythmias. Mutations in 12 genes encoding ion channels and associated proteins are linked with congenital LQTS. With a computational systems biology approach, we found that gene products involved in LQTS formed a distinct functional neighborhood within the human interactome. Other diseases form similarly selective neighborhoods, and comparison of the LQTS neighborhood with other disease-centered neighborhoods suggested a molecular basis for associations between seemingly unrelated diseases that have increased risk of cardiac complications. By combining the LQTS neighborhood with published genome-wide association study data, we identified previously unknown single-nuclScience signalingSystems pharmacology of arrhythmias.PMC3068558DK038761P50 GM071558T32 GM062754UL1RR029887P50GM07558UL1 RR029887R01 DK038761GM062754Iyengar RBerger SIMa'ayan AfalseSystems pharmacology of arrhythmias.Long QT syndrome (LQTS) is a congenital or drug-induced change in electrical activity of the heart that can lead to fatal arrhythmias. Mutations in 12 genes encoding ion channels and associated proteins are linked with congenital LQTS. With a computational systems biology approach, we found that gene products involved in LQTS formed a distinct functional neighborhood within the human interactome. Other diseases form similarly selective neighborhoods, and comparison of the LQTS neighborhood with other disease-centered neighborhoods suggested a molecular basis for associations between seemingly unrelated diseases that have increased risk of cardiac complications. By combining the LQTS neighborhood with published genome-wide association study data, we identified previously unknown single-nucl2010-01-01T00:00:00Z2010 Apr2026-05-05T06:14:12.058Z2019-03-27T00:40:16ZS-EPMC30685582040712510.1126/scisignal.2000723