We therefore cannot completely exclude the possibility that the use of PSA or FH in our control selection criteria led to an observed depletion of LoF variants among controls; although this would imply a uniform direction and comparatively high penetrance of effects across a wide range of DNA repair genes and pathways should these associations have been driven exclusively by extraneous variables such as low PSA levels independently of PCa. Here, FH is linked to posterior cortical atrophy.