Moreover, we suggest that if changes in either gene alone were sufficient to confer AMD susceptibility, one might have expected to discover rare alleles that recapitulate the effect of the in/del (such as rare loss of function mutations in LOC387715 or activating mutations in HTRA1), neither of which have been discovered to date by us or by other groups. Here, HTRA1 is linked to age-related macular degeneration.