To increase our knowledge of genetic determinants influencing HR and discover novel loci, especially rare or low frequency coding variants with larger effects, we meta-analysed data from 104 452 individuals of European-ancestry using the Exome Chip, from cohorts that participated in the Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) EKG consortium. The Exome Chip permits a cost-efficient analysis of coding variants derived from sequencing of >12 000 individuals and includes many rare and low-frequency variants (18). We performed a validation experiment using independent replication samples from UK Biobank data, and bioinformatics investigations to gain an understanding of the new HR loci.
