LAUSR

European flat oyster (Ostrea edulis) is an ecologically and economically important marine bivalve, that has been severely affected by the intracellular parasite Bonamia ostreae. In this study, a flat oyster SNP array (~14,000 SNPs) was used to validate previously reported outlier loci for divergent selection associated with B. ostreae exposure in the Northeast Atlantic Area. A total of 134 wild and hatchery individuals from the North Sea, collected in naïve (NV) and long‐term affected (LTA) areas, were analysed. Genetic diversity and differentiation were related to the sampling origin (wild vs. hatchery) when using neutral markers, and to bonamiosis status (NV vs. LTA) when using outlier loci for divergent selection. Two genetic clusters appeared intermingled in all sampling locations when using outlier loci, and their frequency was associated with their bonamiosis status. When both clusters were compared, outlier data sets showed high genetic divergence (FST > 0.25) unlike neutral loci (FST not ≠ 0). Moreover, the cluster associated with LTA samples showed much higher genetic diversity and significant heterozygote excess with outlier loci, but not with neutral data. Most outliers mapped on chromosome 8 (OE‐C8) of the flat oyster genome, supporting a main genomic region underlying resilience to bonamiosis. Furthermore, differentially expressed genes previously reported between NV and LTA strains showed higher mapping density on OE‐C8. A range of relevant immune functions were specifically enriched among genes annotated on OE‐C8, providing hypotheses for resilience mechanisms to an intracellular parasite. The results suggest that marker‐assisted selection could be applied to breed resilient strains of O. edulis to bonamiosis, if lower parasite load and/or higher viability of the LTA genetic cluster following B. ostreae infection is demonstrated.