Skin trait variation impacts quality-of-life, especially for females from the viewpoint of beauty. To investigate genetic variation related to these traits, we conducted a GWAS of various skin phenotypes in 11,311 Japanese women and identified associations for age-spots, freckles, double eyelids, straight/curly hair, eyebrow thickness, hairiness, and sweating. In silico annotation with RoadMap Epigenomics epigenetic state maps and colocalization analysis of GWAS and GTEx Project eQTL signals provided information about tissue specificity, candidate causal variants, and functional target genes. Novel signals for skin-spot traits neighboured AKAP1/MSI2 (rs17833789; P = 2.2 × 10−9), BNC2 (rs10810635; P = 2.1 × 10−22), HSPA12A (rs12259842; P = 7.1 × 10−11), PPARGC1B (rs251468; P = 1.3 × 10−21), and RAB11FIP2 (rs10444039; P = 5.6 × 10−21). HSPA12A SNPs were the only protein-coding gene eQTLs identified across skin-spot loci. Double edged eyelid analysis identified that a signal around EMX2 (rs12570134; P = 8.2 × 10−15) was also associated with expression of EMX2 and the antisense-RNA gene EMX2OS in brain putamen basal ganglia tissue. A known hair morphology signal in EDAR was associated with both eyebrow thickness (rs3827760; P = 1.7 × 10−9) and straight/curly hair (rs260643; P = 1.6 × 10−103). Excessive hairiness signals’ top SNPs were also eQTLs for TBX15 (rs984225; P = 1.6 × 10−8), BCL2 (rs7226979; P = 7.3 × 10−11), and GCC2 and LIMS1 (rs6542772; P = 2.2 × 10−9). For excessive sweating, top variants in two signals in chr2:28.82-29.05 Mb (rs56089836; P = 1.7 × 10−11) were eQTLs for either PPP1CB or PLB1, while a top chr16:48.26–48.45 Mb locus SNP was a known ABCC11 missense variant (rs6500380; P = 6.8 × 10−10). In total, we identified twelve loci containing sixteen association signals, of which fifteen were novel. These findings will help dermatologic researchers better understand the genetic underpinnings of skin-related phenotypic variation in human populations.

Food allergy is an increasingly important health problem in the world. Several genome-wide association studies (GWAS) focused on European ancestry samples have identified food allergy-specific loci in the HLA class II region. We conducted GWAS of self-reported reactivity with common foods using the data from 11011 Japanese women and identified shrimp and peach allergy-specific loci in the HLA-DR/DQ gene region tagged by rs74995702 (P = 6.30 × 10−17, OR = 1.91) and rs28359884 (P = 2.3 × 10−12, OR = 1.80), respectively. After HLA imputation using a Japanese population-specific reference, the most strongly associated haplotype was HLA-DRB1*04:05-HLA-DQB1*04:01 for shrimp allergy (P = 3.92 × 10−19, OR = 1.99) and HLA-DRB1*09:01-HLA-DQB1*03:03 for peach allergy (P = 1.15 × 10−7, OR = 1.68). Additionally, both allergies’ associated variants were eQTLs for several HLA genes, with HLA-DQA2 the single eQTL gene shared between the two traits. Our study suggests that allergy to certain foods may be related to genetic differences that tag both HLA alleles having particular epitope binding specificities as well as variants modulating expression of particular HLA genes. Investigating this further could increase our understanding of food allergy aetiology and potentially lead to better therapeutic strategies for allergen immunotherapies.

Traits related to primary and secondary sexual characteristics greatly impact females during puberty and day-to-day adult life. Therefore, we performed a GWAS analysis of 11,348 Japanese female volunteers and 22 gynecology-related phenotypic variables, and identified significant associations for bust-size, menstrual pain (dysmenorrhea) severity, and menstrual fever. Bust-size analysis identified significant association signals in CCDC170-ESR1 (rs6557160; P = 1.7 × 10−16) and KCNU1-ZNF703 (rs146992477; P = 6.2 × 10−9) and found that one-third of known European-ancestry associations were also present in Japanese. eQTL data points to CCDC170 and ZNF703 as those signals’ functional targets. For menstrual fever, we identified a novel association in OPRM1 (rs17181171; P = 2.0 × 10−8), for which top variants were eQTLs in multiple tissues. A known dysmenorrhea signal near NGF replicated in our data (rs12030576; P = 1.1 × 10−19) and was associated with RP4-663N10.1 expression, a putative lncRNA enhancer of NGF, while a novel dysmenorrhea signal in the IL1 locus (rs80111889; P = 1.9 × 10−16) contained SNPs previously associated with endometriosis, and GWAS SNPs were most significantly associated with IL1A expression. By combining regional imputation with colocalization analysis of GWAS/eQTL signals along with integrated annotation with epigenomic data, this study further refines the sets of candidate causal variants and target genes for these known and novel gynecology-related trait loci.