full dosage compensation, the variance attributable to the X-chromosome for females was 0.61% (s.e. = 0.32%), 0.82% (s.e. = 0.35%), 0.57% (s.e. = 0.52%) and 0.0% (s.e. = 0.48%) for height, BMI, vWF and QTi, respectively. To verify that we detect heterogeneous variances on the X-chromosome rather than autosomal variance differences between males and females, we fitted the same dosage compensation models for the autosomes. As expected, the equal variance model fitted the data best and the full dosage compensation model was the worst fit for all the traits (Supplementary Table 6). Therefore, the data are consistent with twice as much additive genetic variation for height, BMI, and vWF on the X-chromosome in males as in females, which is predicted from theory under the assumption of random X-inactivation25. While there are syndromic examples illustrating the phenotypic effect of the Lyon hypothesis (e.g., Turner’s syndrome and Kleinfelter syndrome), to our knowledge, this is the first empirical evidence from genotype-phenotype associations on complex traits that the amount of genetic variation on the X-chromosome appears consistent with X-chromosome inactivation. However, the evidence is indirect and not overwhelming. Larger samples sizes and the detection of multiple associated loci on the X-chromosome will be necessary
