ArticleCell genomics2023
Amplification is the primary mode of gene-by-sex interaction in complex human traits.
Article in Cell genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Better together against genetic heterogeneity: A sex-combined joint main and interaction analysis of 290 quantitative traits in the UK Biobank.PLoS genetics · 2024Pooled it
- Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sex.EBioMedicine · 2023Pooled it
- GeneSIS: enhancing transferability of polygenic scores with variant-level gene-by-sex interaction effects.bioRxiv : the preprint server for biology · 2026Article
- Pervasive interactions between exposures and polygenic risk can inform more effective clinical and behavioral interventions.Nature genetics · 2026Article
- A study of sex-specific genetic effects underlying risk of orofacial clefts also highlights the potential impact of sequencing errors due to short read mis-mapping.medRxiv : the preprint server for health sciences · 2026Article
- Article
- Chromosome-specific drift under stabilizing selection generates polygenic barriers to sex chromosome turnover.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beyond Mendel: a call to revisit the genotype-phenotype map through new experimental paradigms.Genetics · 2026Article
- The geometry of G × E: How scaling and endogenous treatment effects shape interaction direction.PLoS genetics · 2026Article
- Transcriptional mechanisms of sex-biased gene expression and their connections to disease-associated variation.Human molecular genetics · 2026Article
- Representation in genetic studies affects inference about genetic architecture.bioRxiv : the preprint server for biology · 2026Article
- Polygenic scores capture genetic modification of the adiposity-cardiometabolic risk factor relationship.Cell genomics · 2026Article
- Effects of testosterone on gene expression in males and females across 40 human tissues.Scientific reports · 2026Article
- Choice of phenotype scale is critical in biobank-based G×E tests.bioRxiv : the preprint server for biology · 2026Article
- Pathway-specific polygenic scores substantially increase the discovery of gene-adiposity interactions impacting liver biomarkers.HGG advances · 2026Article
- Global patterns of natural selection inferred using ancient DNA.bioRxiv : the preprint server for biology · 2026Article
- Drivers of systemic male-female allele frequency divergence in humans.bioRxiv : the preprint server for biology · 2026Article
- Methods for modeling gene-environment interplay using polygenic risk scores.Statistical applications in genetics and molecular biology · 2026Review
- Polygenic prediction of human complex traits using ancient DNA.Current opinion in genetics & development · 2025Review
- The relationship between sexual dimorphism and intersex correlation: do models support intuition?Genetics · 2025Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Sex differences in complex traits are suspected to be in part due to widespread gene-by-sex interactions (GxSex), but empirical evidence has been elusive. Here, we infer the mixture of ways in which polygenic effects on physiological traits covary between males and females. We find that GxSex is pervasive but acts primarily through systematic sex differences in the magnitude of many genetic effects ("amplification") rather than in the identity of causal variants. Amplification patterns account for sex differences in trait variance. In some cases, testosterone may mediate amplification. Finally, we develop a population-genetic test linking GxSex to contemporary natural selection and find evidence of sexually antagonistic selection on variants affecting testosterone levels. Our results suggest that amplification of polygenic effects is a common mode of GxSex that may contribute to sex differences and fuel their evolution.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.