Genetic and environmental factors affecting hair density in East Asian populations.

Background: Hair density traits, including follicular unit density (FUD) and hairs per follicular unit (HFU), are influenced by environmental and genetic factors. Understanding these determinants can refine our knowledge of hair growth patterns and enable more targeted interventions. Historically, large-scale research has been constrained by difficulties in precise phenotyping.

Objectives: To identify environmental and genetic factors associated with hair density in East Asian populations and to explore shared genetic influences among other hair traits and hair disorders.

Methods: We performed quantitative assessments of FUD and HFU using trichoscopic images from 5735 East Asian individuals. Accurate phenotyping was achieved through deep learning-based analyses with manual correction. We used multiple regression to evaluate demographic, lifestyle and reproductive factors, and conducted genome-wide association studies (GWAS), meta-analysis and a combined GWAS (C-GWAS) for hair density, hair curliness, eyebrow thickness and beard thickness. Significant associations were compared with published results on male pattern baldness (MPB). Gene-finasteride use interactions were evaluated via mixed linear models in longitudinal UK Biobank data.

Results: Age, sex, body mass index and menopausal status were significantly associated with FUD and HFU. Three genetic loci, rs11940736 at 4q28.1 (near SPRY1), rs10908366 at 1p34.3 (near RSPO1) and rs3771033 at 2q23.3 (intron NRP2), showed significant associations with hair density, with functional annotations implicating these genes in hair follicle development. In particular, rs3771033 was a significant expression quantitative trait locus for NRP2, where the T allele correlated with lower NRP2 expression but higher FUD. We also found substantial genetic overlap among hair density traits, hair curliness, eyebrow thickness, beard thickness and MPB. In UK Biobank analyses, rs3771033 exhibited allele-specific treatment effects on finasteride response in MPB.

Conclusions: We identified three loci that shape hair density in East Asian populations. Our results clarify the genetic and environmental architecture underlying hair density traits and suggest that genotype-specific responses to finasteride may open new avenues for the personalized management of hair disorders.