Table 2.
Characteristics of the most significant GWAS SNPs associated with rosacea symptom severity score
| rsID | Chromosome position | Allele | MAF | Gene context | Possible effector gene(s) | P value | Effect β (95% CI) | Gene description | Prior published associations with index SNP or SNP(s) within 500 kb and moderate LD (r2 > 0.5) |
|---|---|---|---|---|---|---|---|---|---|
| rs12203592 | 6p25.3: 396321 | C/T | 0.174 | [IRF4] | IRF4 | 1.5 × 10−17 | 0.221 (0.169, 0.273) | Interferon regulatory factor 4 | Hair color (14,35,36), eye color (14,35), skin color (14), freckling (35), non-melanoma skin cancer (36), sunburns/tanning (14,36) |
| rs57390839 | 6p21.32: 32900383 | TT/– | 0.07 | PSMB9–[]- HLA-DMB | HLA-DMA, HLA-DMB | 2.2 × 10−15 | –0.303 (–0.380, –0.227) | HLA class II histocompatibility antigen | Autoimmune and inflammatory disease (21) |
| rs1129038 | 15q13.1: 28356859 | C/T | 0.266 | [HERC2] | OCA2, HERC2 | 4.2 × 10−12 | 0.157 (0.111, 0.202) | Probable E3 ubiquitin-protein ligase | Generalized vitiligo (40), tanning (36), eye color (35,36,57–61), hair color (14,35,36,57) |
| rs16891982 | 5p13.2: 33951693 | C/G | 0.042 | [SLC45A2] (MATP) | SLC45A2 | 1.7 × 10−10 | 0.317 (0.218, 0.202) | Solute carrier family 45 member 2 | Hair color (14,35), eye color (35), skin pigmentation (64), tanning (65), malignant melanoma (66) |
| rs847 | 5q31.1: 131996669 | C/T | 0.2 | [IL13] | IL13 | 2.8 × 10−9 | –0.143 (–0.191, –0.095) | Interleukin 13 | Asthma (23,24), atopic dermatitis (25,26), psoriasis (28), self-reported allergy (27), Hodgkin’s lymphoma (62), IgE levels (63) |
| rs149851565 | 14q31.1: 80509104 | C/A | 0.116 | NRXN3—[]—DIO2 | 4.1 × 10−9 | 0.175 (0.115, 0.235) | No previous associations | ||
| rs77779142 | 11q13.1: 65599656 | C/T | 0.159 | OVOL1–[]-SNX32 | 1.2 × 10−8 | 0.150 (0.097, 0.203) | IBD (18) | ||
| rs1805007 | 16q24.3: 89986117 | C/T | 0.074 | TCF25-[]-TUBB3 | MC1R | 1.3 × 10−7 | 0.189 (0.117, 0.261) | Melanocortin 1 receptor | Hair color (14,36,57), skin sensitivity to sun (57), tanning (36), freckling (35,57), basal cell carcinoma (67), non-melanoma skin cancer (36), melanoma (66,68,69), homocysteine levels (70) |
The table of index or most significant SNPs in each associated locus. Regions were defined by identifying SNPs with P < 1 × 10−5, then grouping these into intervals separated by gaps of at least 250 kb, and choosing the SNP with smallest p within each interval. Mapping and gene context was based on NCBI Build 37, and the gene context for the most likely genes were derived using the HG19 release of the UCSC Known Genes tables. The gene context field has the following interpretations: Gene1, Gene2: The SNP is contained within the transcripts of the specified gene(s); Gene1−[]−Gene2: The SNP is flanked by Gene1 and Gene2. Dashes indicate distance: ‘−’= <10 kb, ‘−−’= <100 kb, ‘−−−’= <1000 kb. The two SNP alleles are in order of major/minor allele. Putative effector genes at each locus were identified by first defining the credible set of SNPs via PICS, and then annotating variants and genes within each credible set using functional fine mapping, differential expression analysis, and prior evidence of association.