Local genetic sex differences in quantitative traits
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62504-4 |
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| _version_ | 1849332254435704832 |
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| author | Emil Uffelmann Christiaan de Leeuw Marijn Schipper Danielle Posthuma |
| author_facet | Emil Uffelmann Christiaan de Leeuw Marijn Schipper Danielle Posthuma |
| author_sort | Emil Uffelmann |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8bd7c5c8cb004ce6ab441f9a16a97dea |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8bd7c5c8cb004ce6ab441f9a16a97dea2025-08-20T03:46:15ZengNature PortfolioNature Communications2041-17232025-08-0116111210.1038/s41467-025-62504-4Local genetic sex differences in quantitative traitsEmil Uffelmann0Christiaan de Leeuw1Marijn Schipper2Danielle Posthuma3Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit AmsterdamDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit AmsterdamDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit AmsterdamDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit AmsterdamAbstract 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.https://doi.org/10.1038/s41467-025-62504-4 |
| spellingShingle | Emil Uffelmann Christiaan de Leeuw Marijn Schipper Danielle Posthuma Local genetic sex differences in quantitative traits Nature Communications |
| title | Local genetic sex differences in quantitative traits |
| title_full | Local genetic sex differences in quantitative traits |
| title_fullStr | Local genetic sex differences in quantitative traits |
| title_full_unstemmed | Local genetic sex differences in quantitative traits |
| title_short | Local genetic sex differences in quantitative traits |
| title_sort | local genetic sex differences in quantitative traits |
| url | https://doi.org/10.1038/s41467-025-62504-4 |
| work_keys_str_mv | AT emiluffelmann localgeneticsexdifferencesinquantitativetraits AT christiaandeleeuw localgeneticsexdifferencesinquantitativetraits AT marijnschipper localgeneticsexdifferencesinquantitativetraits AT danielleposthuma localgeneticsexdifferencesinquantitativetraits |