Extended Data Fig. 1: Overview of the study design.

We utilized a logistic mixed-model for the association analysis, followed by meta-analyses to combine multiple cohorts. Multiple cohorts serve the purpose of replication. Two large cohorts at Broad Institute of different exome capture platforms were used to discover candidate variants (Nextera WES and Twist WES). Two independent cohorts at Sanger (Sanger WGS and Sanger WES) and one Kiel/Regeneron cohort (Regeneron WES) were used to replicate the findings.