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

Jai-Sing Yang; Ting-Yuan Liu; Yu-Chia Chen; Shih-Chang Tsai; Yu-Jen Chiu; Chi-Chou Liao; Fuu-Jen Tsai

doi:10.2147/CCID.S428788

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

Clin Cosmet Investig Dermatol. 2023 Sep 21:16:2597-2612. doi: 10.2147/CCID.S428788. eCollection 2023.

Authors

Jai-Sing Yang^#¹, Ting-Yuan Liu^#², Yu-Chia Chen², Shih-Chang Tsai³, Yu-Jen Chiu^{4

5}, Chi-Chou Liao², Fuu-Jen Tsai^{6

7

8}

Affiliations

¹ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, Taiwan.
² Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, 404327, Taiwan.
³ Department of Biological Science and Technology, China Medical University, Taichung, 406040, Taiwan.
⁴ Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112201, Taiwan.
⁵ Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
⁶ School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404333, Taiwan.
⁷ China Medical University Children's Hospital, Taichung, 404327, Taiwan.
⁸ Department of Medical Genetics, China Medical University Hospital, Taichung, 404327, Taiwan.

^# Contributed equally.

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.

Keywords: HLA genotypes; alopecia areata; genome-wide association study; network analysis.

Grants and funding

This work was supported in part of the project (DMR-112-135 and DMR-112-140) from China Medical University Hospital, Taiwan. This work was also supported in part of the project (MOST 111-2314-B-075 −083 -MY2) from the Ministry of Science and Technology, Taiwan.