Fig. 1

Discovery strategy for LSL cohort. Imposing a candidate list, constructed independently, of a priori disease gene candidates on rare-variant exome-wide analyses, with integration of pedigree information, facilitates genes discovery. LOF putative loss-of-function variants, DNS damaging non-synonymous variation predicted by > 3 of 6 predictive algorithms, ARIC Atherosclerosis Risk in Communities, ExAC Exome Aggregation Consortium, EVS Exome Variant Server, OP ratio of observed to potential LOF alleles, RVIS residual variation intolerance score; *includes de novo and inherited dominant alleles