Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Institute for Genomic Statistics and Bioinformatics, University of Bonn, Bonn, Germany.
Nat Commun. 2023 Sep 22;14(1):5492. doi: 10.1038/s41467-023-41186-w.
Male-pattern hair loss (MPHL) is common and highly heritable. While genome-wide association studies (GWAS) have generated insights into the contribution of common variants to MPHL etiology, the relevance of rare variants remains unclear. To determine the contribution of rare variants to MPHL etiology, we perform gene-based and single-variant analyses in exome-sequencing data from 72,469 male UK Biobank participants. While our population-level risk prediction suggests that rare variants make only a minor contribution to general MPHL risk, our rare variant collapsing tests identified a total of five significant gene associations. These findings provide additional evidence for previously implicated genes (EDA2R, WNT10A) and highlight novel risk genes at and beyond GWAS loci (HEPH, CEPT1, EIF3F). Furthermore, MPHL-associated genes are enriched for genes considered causal for monogenic trichoses. Together, our findings broaden the MPHL-associated allelic spectrum and provide insights into MPHL pathobiology and a shared basis with monogenic hair loss disorders.
男性型脱发（MPHL）很常见，且具有高度遗传性。虽然全基因组关联研究（GWAS）已经深入了解了常见变异对 MPHL 病因的贡献，但稀有变异的相关性仍不清楚。为了确定稀有变异对 MPHL 病因的贡献，我们对 72469 名英国生物库男性参与者的外显子组测序数据进行了基于基因和单变体的分析。虽然我们的人群风险预测表明稀有变异对一般 MPHL 风险的贡献很小，但我们的稀有变异折叠测试总共确定了五个显著的基因关联。这些发现为先前涉及的基因（EDA2R、WNT10A）提供了额外的证据，并突出了 GWAS 位点内外的新的风险基因（HEPH、CEPT1、EIF3F）。此外，与 MPHL 相关的基因在单基因毛发缺失症中被认为是致病基因。总之，我们的发现拓宽了与 MPHL 相关的等位基因谱，并深入了解了 MPHL 的病理生物学及其与单基因脱发疾病的共同基础。
