We show that loss of LOC387715 is likely necessary but not sufficient to explain AMD susceptibility and that a common disease haplotype including the in/del and rs11200638 also has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data, which implicate increased HTRA1 expression in the pathogenesis of AMD, suggest that the AMD risk conferred by this region is potentially driven by multiple variants, and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits. The gene discussed is HTRA1; the disease is age-related macular degeneration.