Characterizing the genetic basis of Cardio-Renal-Metabolic multimorbidity using multivariate genomic modelling

Cardio-renal-metabolic multimorbidity (CRMM) encompasses interrelated conditions affecting the heart, kidneys, and metabolic systems. Researchers conducted the largest multivariate genome-wide association study of CRMM across seven biobanks involving 353,130 participants of European ancestry, 75,436 of African ancestry, and 164,373 of East Asian ancestry. They identified 287 lead genetic loci in the European population, 30 in African ancestry, and 202 in East Asian ancestry. Cross-ancestry analyses revealed population-specific signals and 24 shared loci mapping to FTO and TCF7L2 genes. The study identified candidate drugs used for treating type 2 diabetes and high blood pressure. Mendelian randomization supported causal links with various diseases, and polygenic risk scores demonstrated improved prediction across ancestries.