Genome‐wide association study of psoriasis in an Egyptian population

Abstract

Psoriasis is a chronic inflammatory disorder of the skin, with genetic factors reportedly involved in the disease pathogenesis. Numerous studies reported psoriasis candidate genes. However, these tend to involve mostly in the European and Asian populations. Here, we report the first genome‐wide association study (GWAS) in an Egyptian population, identifying susceptibility variants for psoriasis using a two‐stage case‐control design. In the first discovery stage, we carried out a genome‐wide association analysis using the Infinium® Global Screening Array‐24 v1.0, on 253 cases and 449 control samples of Egyptian descent. In the second replication stage, 26 single‐nucleotide polymorphisms (SNPs) were selected for replication in additional 321 cases and 253 controls. In concordance with the findings from previous studies on other populations, we found a genome‐wide significant association between the MHC locus and the disease at rs12199223 (Pcomb = 6.57 × 10−18) and rs1265181 (Pcomb = 1.03 × 10−10). Additionally, we identified a novel significant association with the disease at locus, 4q32.1 (rs12650590, Pcomb = 4.49 × 10−08) in the vicinity of gene GUCY1A3, and multiple suggestive associations, for example rs10832027 (Pcomb = 7.28 × 10−06) and rs3770019 (Pcomb = 1.02 × 10−05). This proposes the existence of important interethnic genetic differences in psoriasis susceptibility. Further studies are necessary to elucidate the downstream pathways of the new candidate loci.

An integrated personal and population-based Egyptian genome reference

“…We investigated the impact of Egyptian ancestry on disease risk assessment by integrating Egyptian variant data with the GWAS catalog 50 , a curated database of GWAS. According to the GWAS catalog, most published GWAS are performed on Europeans 24 , and only a single study has been performed on Egyptians 51 (by one of the co-authors). Furthermore, only 2% of individuals included in GWAS are of African ancestry 24 .…”

Variants in PRKCE and KLC1, Potential Regulators of Type I Psoriasis

“… 38 The literature supports some differences between familial and sporadic cases of psoriasis. 39 Differences in the strength of the association between the mutant gene and family history have been reported for the MHC, including a strong association of HLA-C*06 and HLA-B*27 with psoriasis.…”

Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis

“…In contrast, type 2associated cells, including T H 2 cells, eosinophils, basophils and ILC2 can increase during AD. GWAS analysis (publicly available databases: GWAS database, https://www.ebi.ac.uk/gwas/; GWAS Central, https://www.gwascentral.org/; accessed 15.11.2021; filtered for psoriasis and atopic eczema traits) of the most common SNPs associated with psoriasis (Pso) and atopic dermatitis (AD) are summarised in the Venn diagram rs6913137, rs2853950, rs3130573, rs7756521, rs9263717, rs2233959, rs2524096, rs12199223, rs1265078, rs2249742, rs2853961, and many more [191,192] TNFAIP3 rs582757, rs610604, rs6933987, rs643177 [181,[193][194][195][196] NFKB1A rs8016947 [193,196] IL36RN rs387906914, rs397514629 [75,197,198] LCE3B rs4845454, rs11205044, rs1581803 [64,199,200] LCE3D rs4085613, rs4112788, rs6677595 [193,194,201] AD and psoriasis HLA-A/B AD: rs148203517, rs4713555, rs28752924, rs28383323, rs200291258, rs9405068, rs4713555, rs2251396; Pso: rs4406273, rs2523619, rs17728338, rs75851973, rs76956521, rs1960278, rs12212594, rs4959062, rs4349859, rs10484554 [64,80,172,173,181,191,193,196,202] CARD14 AD: rs535171797; Pso: rs11652075 [193,203] IL12B AD: rs3212227, rs393548, rs436857; Pso: rs2082412, rs3212227, rs3213094, rs2546890, rs12188300, rs12188300, rs6887695 [78,[193][194][195][204][205][206] IL13 AD: rs848, rs1295686, rs847, rs1295685, rs20541, rs12188917; Pso: rs20541, rs1295685, rs847…”