We note that although bi-allelic loss of GJB2 is associated with AR hearing loss, there is a high observed/expected number of pLoF variants in GJB2 in gnomAD, with a LOEUF score of 1.97, higher than 99.9% (5/3064) of AD and/or AR genes, suggesting a possible selective advantage of pLoF variants in GJB2 which has been explored previously31–33. This evidence concerns the gene GJB2 and Alzheimer disease.