Dissection of genetic variation and evidence for pleiotropy in male pattern baldness

• DOI: 10.1038/s41467-018-07862-y
• Publication Date: 2018-12-14T16:21:25Z
• Authors: Chloe X. Yap; Julia Sidorenko; Yang Wu; Kathryn E. Kemper; Jian Yang; Naomi R. Wray; Matthew R. Robinson; Peter M. Visscher
• Keywords: Age Factors; Alopecia/genetics; Bone Density; Genetic Pleiotropy; Genetic Variation; Humans; Linkage Disequilibrium; Polymorphism, Single Nucleotide; United Kingdom; 0303 health sciences; 1300 Biochemistry; Science; Q; 590; Age Factors; General Physics and Astronomy; Genetic Variation; Genetics and Molecular Biology; Alopecia; Genetic Pleiotropy; General Chemistry; 1600 Chemistry; Polymorphism, Single Nucleotide; Article; Linkage Disequilibrium; United Kingdom; 03 medical and health sciences; Bone Density; General Biochemistry; Humans; 3100 Physics and Astronomy

AbstractMale 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.