Genome-Wide Association Study of Alopecia Areata in Taiwan: The Conflict Between Individuals and Hair Follicles

Abstract

Purpose Alopecia areata (AA) is one of the most prevalent autoimmune diseases affecting humans. Given that hair follicles are immune-privileged, autoimmunity can result in disfiguring hair loss. However, the genetic basis for AA in the Taiwanese population remains unknown. Materials and Methods A genome-wide association study was conducted using a cohort of 408 AA cases and 8167 controls. To link variants to gene relationships, we used 882 SNPs (P<1E-05) within 74 genes that were associated with AA group to build the biological networks by IPA software. HLA diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)-R package and chi-square analysis. Results Seven single nucleotide polymorphisms (SNPs) including LINC02006 (rs531166736, rs187306735), APC (rs112800832_C_CAT), SRP19 (rs139948960, rs144784670), EGFLAM (rs16903975) and LDLRAD3 (rs79874564) were closely associated with the AA phenotype (P<5E-08). Examination of biological networks revealed that these genomic areas are associated with antigen presentation signaling, B cell and T cell development, Th1 and Th2 activation pathways, Notch signaling, crosstalk signaling between dendritic cells and natural killer cells, and phagosome maturation. Based on human leukocyte antigen (HLA) genotype analysis, four HLA genotypes (HLA-B*15:01-*40:01, HLA-DQA1*01:02-*03:03, HLA-DQA1*01:02, and HLA-DQB1*02:01) were found to be associated with AA (adjusted p-value<0.05). HLA-DQA1*01:02 is the most significantly related gene in the Taiwanese population (adjusted p-value = 2.09E-05). Conclusion This study successfully identified susceptibility loci associated with AA in the Taiwanese population. These findings not only shed light on the origins of AA within the Taiwanese context but also contribute to a comprehensive understanding of the genetic factors influencing AA susceptibility.

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

“…The association between the SNP array and psoriasis was investigated using PLINK (V.1.90). A Manhattan plot and quantile-quantile plot (QQ) ( ; version 0.1.9) was generated using the R programming language ( ; version: R 4.1.0) within the R Studio ( ; version: R 1.4.1717) integrated development environment ( 38 , 39 ). Table SI presents the GWAS analysis results.…”

“…A molecular network was constructed using core analysis in the IPA software ( ; version: 107193442; Qiagen Sciences, Inc.). The statistical significance of the available networks was assessed using Fisher's exact test with a significance level of P<0.05 ( 39 , 41 , 42 ).…”

“…org/; version: R 4.1.0) within the R Studio (https://posit. co/downloads/; version: R 1.4.1717) integrated development environment (38,39). Table SI presents the GWAS analysis results.…”

“…GWAS, genome-wide association study; HLA, human leukocyte antigen; PRS, polygenic risk score; SNP, single nucleotide polymorphism; IPA, Ingenuity Pathway Analysis; CMUH, China Medical University Hospital; BBJ, BioBank Japan; IQR, interquartile range; PCA, principal component analysis; INFO, imputation quality score; GP, genomic prediction; PheWAS, phenome-wide association. assessed using Fisher's exact test with a significance level of P<0.05 (39,41,42).…”

“…Chi-square analysis was conducted to examine the HLA haplotypes and diplotypes to investigate the association between these genetic factors and the incidence of psoriasis. Bonferroni correction was applied to address multiple testing (39,43). PRS analysis.…”