Original Investigation

Human Genetics

, Volume 126, Issue 2, pp 255-264

Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness

  • Axel M. HillmerAffiliated withDepartment of Genomics, Life and Brain Center, University of BonnGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)Genome Technology and Biology Group, Genome Institute of Singapore Email author 
  • , Jan FreudenbergAffiliated withCenter for Genomics and Human Genetics, Feinstein Institute for Medical Research, Northshore-LIJ Healthsystem
  • , Sean MylesAffiliated withInstitute for Genomic Diversity, Cornell University
  • , Stefan HermsAffiliated withDepartment of Genomics, Life and Brain Center, University of Bonn
  • , Kun TangAffiliated withDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology
  • , David A. HughesAffiliated withDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology
  • , Felix F. BrockschmidtAffiliated withDepartment of Genomics, Life and Brain Center, University of Bonn
  • , Yijun RuanAffiliated withGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR)
  • , Mark StonekingAffiliated withDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology
    • , Markus M. NöthenAffiliated withDepartment of Genomics, Life and Brain Center, University of BonnInstitute of Human Genetics, University of Bonn

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Abstract

Genetic variants in the human androgen receptor gene (AR) are associated with male pattern baldness (androgenetic alopecia, AGA) in Europeans. Previous observations of long-range linkage disequilibrium at the AR locus are consistent with the hypothesis of recent positive selection. Here, we further investigate this signature and its relationship to the AGA risk haplotype. The haplotype homozygosity suggests that the AGA risk haplotype was driven to high frequency by positive selection in Europeans although a low meiotic recombination rate contributed to the high haplotype homozygosity. Further, we find high levels of population differentiation as measured by F ST and a series of fixed derived alleles along an extended region centromeric to AR in the Asian HapMap sample. The predominant AGA risk haplotype also carries the putatively functional variant 57K in the flanking ectodysplasin A2 receptor gene (EDA2R). It is therefore probable that the AGA risk haplotype rose to high frequency in combination with this EDA2R variant, possibly by hitchhiking on a positively selected 57K haplotype.