… , 1 while familial studies identified rare variants in the same genes resulting in … using whole
genome (WGS) and whole exome sequencing (WES) to facilitate the analysis of rare variants…

… By leveraging 10,900 whole-exome sequences linked to … Aggregation of multiple rare variants
in a gene (that is, gene burden… We collapsed rare pLOF variants into gene burdens across …

… rare variant burden over a large number of genes can be combined into a predictive rare
variant … gene-based association, we conducted a series of simulations and determined the CF’s …

… (SKAT), or unified tests that can consider both a burden and … of including rare variants from
exome sequence data in … and identifying associations that could not have been discovered …

… We found that rare variants previously reported as pathogenic accounted for most of the
annotation burden, necessitating time-intensive manual curation of the supporting primary …

… burden, we found that retaining very low frequency variants that occur in <0.1% of the … half
of the variants detected in our study were LOF and/or previously reported variants at the time …

… Exome sequencing has revolutionized our understanding of … Our variant-level association
tests detected rare variant associations … in these genes contributed to disease burden. This is …

… We illustrate the ability of exome sequencing to identify gene–trait associations, elucidate …
We aggregated rare variants for gene burden testing as previously described 39 . In brief, …

… We have initiated WGS of UK Biobank participants to identify rare variant associations with
participants in the extreme tails of a quantitative phenotype who are typically excluded from …

… to the diagnosis of rare diseases poses an immense burden and psychological … for rare
diseases and are incrementally becoming the first-line option for causative variants identification, …