Identification of potential therapeutic targets for hair color and hair shaft abnormalities by integrating human plasma proteomics
10.3760/cma.j.cn114453-20241126-00307
- VernacularTitle:通过整合人血浆蛋白质组学识别毛发颜色和发干异常的潜在治疗靶点
- Author:
Guangdi LI
1
;
Guiwen ZHOU
;
Yichen WANG
;
Xiao XU
;
Minliang CHEN
Author Information
1. 解放军总医院第四医学中心烧伤整形医学部，北京 100853
- Publication Type:Journal Article
- Keywords:
Hair diseases;
Hair color abnormalities;
Hair shaft abnormalities;
Proteomics;
Drug targets;
Genetics;
Colocalization analysis;
Mendelian randomization
- From:
Chinese Journal of Plastic Surgery
2025;41(5):482-491
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, providing novel insights and approaches for managing related conditions.Methods:Using the pQTL data from large-scale proteomics studies, a two-sample Mendelian randomization (TwoSampleMR) was conducted to preliminarily identify potential drug therapeutic targets. Subsequently, sensitivity analysis was performed to evaluate potential confounding factors such as heterogeneity and horizontal pleiotropy, and a leave-one-out sensitivity analysis was conducted by eliminating each single nucleotide polymorphism (SNP) one by one. Finally, co-localization analysis was carried out to explore whether there are shared genetic variants between the identified plasma proteins and traits.Results:The proteomic data used in this study included 4, 907 pQTLs, while the genetic data related to hair pigmentation and shaft abnormalities comprised 124 cases and 432, 686 controls. After Mendelian randomization screening, six candidate protein genes were identified: HLA-DQA2, CTSB, KIR2DS2, SVEP1, HOMER2, and HOMER1. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among these proteins. Leave-one-out sensitivity analysis indicated that no single SNP significantly influenced the overall result. Notably, HOMER2 was supported by colocalization analysis with strong evidence, suggesting its potential role in regulating genetic mechanisms underlying hair pigmentation and shaft health.Conclusions:This study identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 showing stronger evidence. These findings provide novel directions for the treatment of hair color and hair shaft abnormalities.
