A genome-wide association study identified a genetic variant associated with hair thinning in Japanese women.

Hair thinning in women is caused by the complex effects of a number of factors, including aging, the hormonal status, and lifestyle. Hair thinning has a significant impact on psychological and social activities and reduces quality of life; therefore, countermeasures are required. The collection of information on whether an individual is predisposed to hair thinning is important for raising awareness on the need for preventive actions. Genome-wide association studies (GWAS) recently identified genetic regions associated with various conditions, and genetic tests to diagnose such conditions in advance have been attracting increasing interest. Single nucleotide polymorphisms (SNPs) associated with female pattern hair loss (FPHL), one of the causes of hair loss in women, have been identified around genes related to the synthesis and metabolism pathways of steroid hormones and their receptors.1-3 Ohn et al.3 reported the involvement of SNPs in ATP-binding cassette subfamily C member 4 in early onset FPHL as a factor other than steroid hormone-related factors. However, these studies examined Caucasian, Chinese, and Korean populations. Few GWAS have been performed on hair thinning in Japanese women. Therefore, we herein conducted GWAS to identify SNPs involved in hair thinning in Japanese women. A questionnaire survey showed that 10% or less of women in their 20s felt that their hair was thinning; however, this percentage gradually increased with age to 80% or higher in women in and older than their 70s (Figure S1, Table S1). GWAS on all subjects (1040 women aged 21–95 years) identified rs2419385 as a SNP with the strongest signal (p-value = 1.22 × 10−7) (Figure S2a,b, Table S2). Furthermore, when we performed a similar analysis of middle-aged women (926 women aged 30–69 years) by excluding those in their 20s (young age) and those in their 70s and older (old age) in consideration of the condition of hair being markedly affected by age, rs2419385 (p-value = 1.84 × 10−8) fulfilled the genome-wide significance level (p-value = 5.0 × 10−8) (Figure 1A,B, Table S2). An examination of genes near rs2419385 using the Locus Zoom plot (http://locuszoom.org/) revealed the presence of genes including clathrin interactor 1 (CLINT1) and tRNA-histidine guanylyltransferase 1 like (THG1L) (Figure 1c). Moreover, an evaluation of eQTL using FUMA (https://fuma.ctglab.nl/) suggested the involvement of rs2419385 in the expression of CLINT1 and THG1L (Table S3). Although the effects of these genes on hair growth currently remain unknown, both have been suggested to play a role in transforming growth factor beta signaling, which is known to negatively regulate hair growth.4, 5 Future studies are needed to investigate the roles of these genes in hair thinning in more detail. In summary, we herein identified rs2419385 as a SNP associated with hair thinning in Japanese women. This SNP and the genes located near it may provide novel insights into hair thinning in Japanese women. A limitation of the present study was the use of a self-administered questionnaire to collect phenotypic data on subjects. We intend to investigate the mechanisms underlying the onset of hair thinning in future studies by confirming reproducibility using objective data, including diagnoses by dermatologists, and conducting further analyses. RO and SH designed the research. RO, TI, YH, and MKH performed the research and data analysis. RO wrote the manuscript. All authors critically revised the manuscript and approved the final draft. We are indebted to all of the volunteers who participated in the present study. We appreciate the contribution of Yu Inoue (Nippon Menard Cosmetic Co., Ltd., Aichi, Japan) to this study. We also thank Takaaki Yamada, Yuichiro Ogata, Katsuma Miyachi, Masahiro Fujimura, Yoshie Ishii, and Ayumi Sanada (Nippon Menard Cosmetic Co., Ltd., Aichi, Japan) for their assistance with sample processing. The authors declare no conflicts of interest. The present study was approved by the Ethics Review Board of our company. Informed consent for participation in the present study was obtained by providing a sufficient explanation in writing in advance. Author elects to not share data Figure S1: Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.