As IRF4 contributes to the pigmentation of human skin, hair and eye. In geographical areas distant from the equator, less-pigmented skin, hair and eyes have been under positive selection, presumably due to the fact that this optimizes use of available ultraviolet radiation (UVR) for vitamin D3 generation.
We identify 63 MPB-associated loci (P39% 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..
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.
DKK2 encodes for a member of the family of dickkopf WNT-signalling inhibitors, which are reported to be secreted by dermal papilla cells Fig. 2(DPCs) in response to androgens and to promote androgen-induced (premature) anagen-to-catagen transition (Fig. An interesting focus for future research will be to map androgen receptor (AR) binding sites in DPCs and other hair-related cell types to test for enrichment of MPB-risk variants.