Peder Emil Warming, Frederik Nybye Ågesen, Thomas Hadberg Lynge, Rodrigue Garcia, Jytte Banner, Eva Prescott, Theis Lange, Reza Jabbari, Jacob Tfelt-Hansen
The impact of modifiable risk factors in the association between socioeconomic status and sudden cardiac death in a prospective cohort study: equal access to healthcare, unequal outcome
European journal of preventive cardiology
polygenic risk scores prss commonly used predicting individuals genetic risk complex diseases yet implication disease pathogenesis remains largely limited introduce scprs geometric deep learning model constructs singlecellresolved prs leveraging reference singlecell chromatin accessibility profiling data enhance biological discovery well disease prediction realworld applications across multiple complex diseases including type 2 diabetes t2d hypertrophic cardiomyopathy hcm alzheimers disease ad showcase superior prediction power scprs compared traditional prs methods importantly scprs predicts disease risk also uncovers diseaserelevant cells hormonehigh alpha beta cells t2d cardiomyocytes pericytes hcm astrocytes microglia oligodendrocyte progenitor cells ad facilitated layered multiomic analysis scprs identifies celltypespecific genetic underpinnings linking diseaseassociated genetic variants gene regulation within corresponding cell types substantiate disease relevance scprsprioritized hcm genes demonstrate suppression genes hcm cardiomyocytes rescued mavacamten treatment additionally establish novel microgliaspecific regulatory relationship ad risk variant rs7922621 target genes anxa11 tspan14 illustrate detrimental effects suppressing two genes microglia phagocytosis work provides multitasking interpretable framework precise disease prediction systematic investigation genetic cellular molecular basis complex diseases laying methodological foundation singlecell genetics