Local genetic sex differences in quantitative traits

Emil Uffelmann (), Christiaan Leeuw, Marijn Schipper and Danielle Posthuma
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Emil Uffelmann: Vrije Universiteit Amsterdam
Christiaan Leeuw: Vrije Universiteit Amsterdam
Marijn Schipper: Vrije Universiteit Amsterdam
Danielle Posthuma: Vrije Universiteit Amsterdam

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Many traits show small global sex differences in genetic correlations and heritability. However, how these differences are distributed across the genome remains unknown. Here, we use LAVA to test for local genetic sex differences in genetic correlations, heritabilities, and the magnitude of genetic effects across 157 quantitative traits in the UK Biobank. Nearly every trait shows evidence for sex-dimorphic effects in at least one locus. We find that such loci can flag biological differences between the sexes. Moreover, we test for differences in the magnitude of genetic effects on the raw and the standardized scale. We show these have complementary interpretations, where only the latter scale is informative for heritability. Our results show how average metrics of genetic correlation and heritability across the whole genome can mask important variability between loci and that the scale of genetic effects needs to be considered carefully when comparing their magnitudes.

Date: 2025
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DOI: 10.1038/s41467-025-62504-4

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