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.

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.

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Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.