Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07: 02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1 , encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07: 02.

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registered and, of these, 28% accurately reported a preregistered specific outcome. 4 The respective rates in this study (66% and 67%) are a notable improvement. This may reflect that our study assessed only high-impact-factor journals, the continued impact of policies mandating prospective trial registration, 5 and the increasing recognition of the importance of prospective trial registration by dermatology journals. 6 Discerning whether primary outcome discrepancies reflect benign variations in levels of detail or more sinister post hoc selection of results based on significance can be challenging. Of concern, previous work has associated discrepancies with an increased likelihood of larger effect sizes and statistically significant results. 7,8 Currently, the CONSORT guidelines acknowledge that changes to preregistered outcomes can occur, but that in such instances the change and rationale should be detailed in the manuscript. In the absence of an explanation, discrepancies should raise suspicion of bias.

• Pediatric and adult emergencies differ. • Pediatric life-threatening emergencies are not frequent. What is New: • This study is the first to describe a European national cohort of pediatric physician-staffed EMS missions and to compare the pediatric and the adult missions at a national level. • This large cohort study confirms scarce regional data indicating that pediatric pre-hospital emergencies are not frequent and mostly non-life-threatening.

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