In search of intralocus sexual conflict in the multivariate and local genetic architecture of metabolic traits in humans

Despite a common genome, males and females are remarkably different across species. Intralocus Sexual Conflict (IASC) arises when selection favours different trait values in the sexes but a shared genetic architecture constrains their evolutionary divergence. IASC is typically studied at the single-trait level, and genome-wide architectures can obscure conflict localized to specific genomic regions. We investigated IASC in the multivariate and local genetic architecture of 17 human metabolic traits and lifetime reproductive success by estimating the sex-stratified additive genetic (co)variance matrix (Gmf) and local cross-sex-cross-trait genetic correlations. Genome-wide, between-sex covariance matrix (B) showed only 1.15% asymmetry, and sexually concordant (SC) genetic variation exceeded sexually antagonistic (SA) variation by 18.5-fold. Indirect evolutionary response to SC selection was 1.6-fold stronger than direct responses to SA selection. In contrast, local analyses revealed a more heterogeneous structure - among the regions with significant local correlations, 12% were consistently SA, showing opposite fitness effects in the sexes, with functional enrichment in WNT signalling, while 20% exhibited both SA and SC effects. Our results demonstrate that in human metabolic traits, SC variation predominates genome-wide, whereas SA variation is concentrated in specific local regions, highlighting the importance of integrating multivariate and local frameworks in understanding conflict.