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 100048
- 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(7):734-743
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify potential therapeutic targets for the treatment of hair color and hair shaft abnormalities, thereby offering innovative insights and strategies for the management of the associated conditions.Methods:Using the protein quantitative trait locus(pQTL) data derived from extensive proteomics studies, a two-sample Mendelian randomization was conducted to preliminarily identify potential drug therapeutic targets. Following this, sensitivity analyses were performed to evaluate potential confounding factors, including heterogeneity and horizontal pleiotropy. A leave-one-out sensitivity analysis was also conducted, systematically excluding each single nucleotide polymorphism (SNP) to evaluate their individual impact. Additionally, co-localization analysis was carried out to determine the presence of shared genetic variants between the identified plasma proteins and the relevant traits.Results:The proteomic data analyzed in this investigation encompassed 4 907 pQTLs, while the genetic data pertaining to hair pigmentation and shaft abnormalities included 124 cases and 432 686 controls. Through the 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. The leave-one-out sensitivity analysis demonstrated that no single SNP significantly affected the overall findings. Notably, HOMER2 was substantiated by co-localization analysis, which provided robust evidence of its potential role in regulating the genetic mechanisms associated with hair pigmentation and shaft integrity.Conclusion:This study successfully identified six potential therapeutic targets for hair pigmentation and shaft abnormalities, with HOMER2 exhibiting the most compelling evidence. These findings pave the way for novel therapeutic approaches in the treatment of hair color and hair shaft disorders.
