Original Investigation

Human Genetics

, Volume 118, Issue 6, pp 691-694

First online:

Extreme skewing of X chromosome inactivation in mothers of homosexual men

  • Sven BocklandtAffiliated withDepartment of Human Genetics, University of CaliforniaLaboratory of Biochemistry, National Cancer Institute Email author 
  • , Steve HorvathAffiliated withDepartment of Human Genetics, University of CaliforniaDepartment of Biostatistics, University of California
  • , Eric VilainAffiliated withDepartment of Human Genetics, University of California
  • , Dean H. HamerAffiliated withLaboratory of Biochemistry, National Cancer Institute

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Human sexual preference is a sexually dimorphic trait with a substantial genetic component. Linkage of male sexual orientation to markers on the X chromosome has been reported in some families. Here, we measured X chromosome inactivation ratios in 97 mothers of homosexual men and 103 age-matched control women without gay sons. The number of women with extreme skewing of X-inactivation was significantly higher in mothers of gay men (13/97=13%) compared to controls (4/103=4%) and increased in mothers with two or more gay sons (10/44=23%). Our findings support a role for the X chromosome in regulating sexual orientation in a subgroup of gay men.