Figure 2.

Overview of the cohorts and rare variant burden analyses performed in this study. The primary cohort (n=1040) was compared with 912 healthy controls sequenced on the same platform and with the Exome Aggregation Consortium (ExAC) reference dataset. A further 1498 cases were sequenced in diagnostic laboratories on a range of platforms over a decade, and compared with ExAC (n=60 706). Comparing both cohorts with the ExAC reference population dataset, extensive quality control was performed to minimize differences caused by sequencing technologies.