Association between a 46-SNP Polygenic Risk Score and melanoma risk in Dutch patients with familial melanoma

Background Familial clustering of melanoma suggests a shared genetic predisposition among family members, but only 10%–40% of familial cases carry a pathogenic variant in a known high-risk melanoma susceptibility gene. We investigated whether a melanoma-specific Polygenic Risk Score (PRS) is associated with melanoma risk in patients with genetically unexplained familial melanoma. Methods Dutch familial melanoma cases (n=418) were genotyped for 46 SNPs previously identified as independently associated with melanoma risk. The 46-SNP PRS was calculated and standardised to 3423 healthy controls (sPRS) and the association between PRS and melanoma risk was modelled using logistic regression. Within the case series, possible differences were further explored by investigating the PRS in relation to (1) the number of primary melanomas in a patient and (2) the extent of familial clustering of melanoma. Results The PRS was significantly associated with melanoma risk, with a per-SD OR of 2.12 (95% CI 1.90 to 2.35, p<0.001), corresponding to a 5.70-fold increased risk (95% CI 3.93 to 8.28) when comparing the top 90th to the middle 40–60th PRS percentiles. The mean PRS was significantly higher in cases with multiple primary melanomas than in cases with a single melanoma (sPRS 1.17 vs 0.71, p=0.001). Conversely, cases from high-density melanoma families had a lower (but non-significant) mean PRS than cases from low-density families (sPRS 0.60 vs 0.94, p=0.204). Conclusion Our work underlines the significance of a PRS in determining melanoma susceptibility and encourages further exploration of the diagnostic value of a PRS in genetically unexplained melanoma families

The interconnections between maternal and newborn health--evidence and implications for policy

The past decade has witnessed increasing global attention and political support for maternal, newborn and child health. Despite this increased attention, actual progress has been slow and sporadic: coverage of key maternal and newborn health interventions remains low and there are wide disparities in access to care, within and across countries. Strategies for improving maternal and newborn health are closely linked, and can be delivered most effectively through a continuum of care approach. While these interventions are largely known, there is little information on which interventions have a positive health impact for both women and newborns. This supplement identifies the interventions during the preconception, pregnancy, intrapartum and postnatal periods found to have a positive, synergistic effect on maternal and neonatal outcomes. These interventions are then grouped into packages of care for delivery at the community, health center or hospital levels