
Summary Quantitative genetics theory predicts that X-chromosome dosage compensation between sexes will have a detectable effect on the amount of genetic and therefore phenotypic trait variances at associated loci in males and females. Here, we systematically examine the role of dosage compensation in complex trait variation in humans in 20 complex traits in a sample of more than 450,000 individuals from the UK Biobank and in 1,600 gene expression traits from a sample of 2,000 individuals as well as across-tissue gene expression from the GTEx resource. We find, on average, twice as much genetic variation for complex traits due to X-linked loci in males compared to females, consistent with a negligible effect of predicted escape from X-inactivation on complex trait variation across traits and also detect biologically relevant X-linked heterogeneity between the sexes for a number of complex traits.
Male, Multifactorial Inheritance, 1300 Biochemistry, Science, 590, Chromosome Inactivation, Gene-Expression, Datasets as Topic, Genetics and Molecular Biology, Article, Sex Factors, 1300 Biochemistry, Genetics and Molecular Biology, Genes, X-Linked, X Chromosome Inactivation, Xist Rna, Humans, 3100 Physics and Astronomy, Variability, Models, Genetic, Q, Variants, Genetic Variation, 1600 Chemistry, Phenotype, Genetic Loci, Sex, Female, Eqtl, Gwas, Genome-Wide Association Study
Male, Multifactorial Inheritance, 1300 Biochemistry, Science, 590, Chromosome Inactivation, Gene-Expression, Datasets as Topic, Genetics and Molecular Biology, Article, Sex Factors, 1300 Biochemistry, Genetics and Molecular Biology, Genes, X-Linked, X Chromosome Inactivation, Xist Rna, Humans, 3100 Physics and Astronomy, Variability, Models, Genetic, Q, Variants, Genetic Variation, 1600 Chemistry, Phenotype, Genetic Loci, Sex, Female, Eqtl, Gwas, Genome-Wide Association Study
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