Uffelmann Emil, de Leeuw Christiaan, Schipper Marijn, Posthuma Danielle
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Child and Adolescent Psychiatry and Pediatric Psychology, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Nat Commun. 2025 Aug 6;16(1):7232. doi: 10.1038/s41467-025-62504-4.
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.
许多性状在遗传相关性和遗传力方面表现出微小的整体性别差异。然而，这些差异如何在基因组中分布仍不清楚。在这里，我们使用LAVA来测试英国生物银行中157个数量性状在遗传相关性、遗传力以及遗传效应大小方面的局部遗传性别差异。几乎每个性状在至少一个基因座上都显示出性别二态性效应的证据。我们发现这些基因座可以标记出两性之间的生物学差异。此外，我们测试了原始尺度和标准化尺度上遗传效应大小的差异。我们表明这些具有互补的解释，其中只有后一种尺度对遗传力有参考价值。我们的结果表明，全基因组遗传相关性和遗传力的平均指标如何掩盖了基因座之间重要的变异性，并且在比较遗传效应大小时需要仔细考虑遗传效应的尺度。
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