Abstract
Male pattern baldness (MPB) is a sex-limited, age-related, complex trait. We study MPB genetics in 205,327 European males from the UK Biobank. Here we show that MPB is strongly heritable and polygenic, with pedigree-heritability of 0.62 (SE = 0.03) estimated from close relatives, and SNP-heritability of 0.39 (SE = 0.01) from conventionally-unrelated males. We detect 624 near-independent genome-wide loci, contributing SNP-heritability of 0.25 (SE = 0.01), of which 26 X-chromosome loci explain 11.6%. Autosomal genetic variance is enriched for common variants and regions of lower linkage disequilibrium. We identify plausible genetic correlations between MPB and multiple sex-limited markers of earlier puberty, increased bone mineral density (rg = 0.15) and pancreatic β-cell function (rg = 0.12). Correlations with reproductive traits imply an effect on fitness, consistent with an estimated linear selection gradient of -0.018 per MPB standard deviation. Overall, we provide genetic insights into MPB: a phenotype of interest in its own right, with value as a model sex-limited, complex trait.
Highlights
Male pattern baldness (MPB) is a sex-limited, age-related, complex trait
Estimates of variance explained by genome-wide autosomal SNPs (h2SNP) range from 0.34 to 0.674,8. (See Box[1] for an overview of heritability definitions.) The Xq12 locus within the androgen receptor gene (AR) was the first locus to be linked to MPB9, and was replicated across different populations[10], in linkage analysis[11] and in genome-wide association studies (GWAS)[4,8,12,13,14]
Our GWAS shows that MPB is highly polygenic, and we find associations with other sex-limited traits and bone mineral density that suggest pleiotropy
Summary
Male pattern baldness (MPB) is a sex-limited, age-related, complex trait. We study MPB genetics in 205,327 European males from the UK Biobank. (See Box[1] for an overview of heritability definitions.) The Xq12 locus within the androgen receptor gene (AR) was the first locus to be linked to MPB9, and was replicated across different populations[10], in linkage analysis[11] and in genome-wide association studies (GWAS)[4,8,12,13,14]. Three large-scale MPB GWAS studies were published in 2017, significantly increasing the number of candidate loci. HeilmannHeimbach et al.[4] performed a GWAS case-control meta-analysis on over 22,000 males, finding 63 independent MPB-associated loci, with six on the X-chromosome. All three studies use different definitions for distinct loci, so the reported numbers are difficult to compare
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