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荟萃分析确定了新的风险基因座,并为男性型秃发的生物学提供了系统的见解。

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness.

机构信息

Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.

Department of Genomics, Life &Brain Center, University of Bonn, 53127 Bonn, Germany.

出版信息

Nat Commun. 2017 Mar 8;8:14694. doi: 10.1038/ncomms14694.

Abstract

Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10, METAL) of which 23 have not been reported previously. The 63 loci explain ∼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the development of novel therapeutic options. The data provide molecular evidence that rather than being an isolated trait, MPB shares a substantial biological basis with numerous other human phenotypes and may deserve evaluation as an early prognostic marker, for example, for prostate cancer, sudden cardiac arrest and neurodegenerative disorders.

摘要

男性型脱发(MPB)是一种常见的、高度遗传性的特征,表现为雄激素依赖性、头皮渐进性脱发。在这里,我们进行了迄今为止最大的男性型脱发全基因组关联研究荟萃分析,包括来自八个独立队列的 10846 例早发性病例和 11672 例对照。我们确定了 63 个与 MPB 相关的位点(P<5 × 10,METAL),其中 23 个以前没有报道过。这 63 个位点解释了 MPB 表型变异的约 39%,并突出了几个合理的候选基因(FGF5、IRF4、DKK2)和途径(褪黑素信号、脂肪生成),这些基因和途径可能与 MPB 的关键病理生理特征有关,可能是开发新治疗选择的有前途的靶点。这些数据提供了分子证据,表明 MPB 不是一种孤立的特征,而是与许多其他人类表型有很大的生物学基础,可能值得作为早期预后标志物进行评估,例如前列腺癌、心源性猝死和神经退行性疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3eca/5344973/38d9cb9f9ae5/ncomms14694-f1.jpg

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