The hard clam, Mercenaria mercenaria, is among the most economically- and ecologically-important marine species in the United States. Several Northeastern states have suffered severe losses in hard clam stocks due to a fatal disease caused by a protistan parasite called Quahog Parasite Unknown (QPX). Previous research clearly showed that the susceptibility of clams to QPX disease is a heritable trait. Here, we generated a draft genome of the clam and used ddRADSeq methods to identify SNPs associated with disease resistance. DNA was extracted from clams derived from two geographically segregated populations and deployed in the same enzootic site in Massachusetts. The analysis contrasted samples collected before and after undergoing QPX-related mortalities. As a result, around 200 genes displayed significant variant enrichment at each sampling point including 18 genes shared between both populations. Markers depleted in survivors from both populations were in genes related to apoptosis pathways, suggesting a role for apoptosis regulation in survivorship. Markers enriched in survivors from both populations were found in genes related to protein-protein interactions, receptors, and signaling. Although more research is needed to identify the precise physiological mechanisms linked to resistance, our study will help develop selective breeding for resistant stocks.