@article{20848,
  abstract     = {Genetic variation that influences complex disease susceptibility is introduced into the population by mutation and removed by natural selection and genetic drift. This mutation–selection–drift balance (MSDB) shapes the prevalence of a disease and its genetic architecture. To date, however, MSDB has been modeled only for monogenic (Mendelian) diseases. Here, we develop an MSDB model for complex disease susceptibility: we assume that genotype relates to disease risk according to the canonical liability threshold model and that the selection on variants affecting risk stems from the fitness cost of the disease. We focus on diseases that are highly polygenic, entail a substantial fitness cost, and are neither extremely common in the population nor exceedingly rare. The comparison of model predictions with genome-wide association studies and other observations in humans indicates that common genetic variation affecting complex disease susceptibility is little affected by directional selection and instead shaped by pleiotropic stabilizing selection on other traits. In turn, directional selection may exert a more substantial effect on rare, large-effect variants. Our results also suggest that current estimates of disease heritability are likely biased. The model thus provides a better understanding of the evolutionary processes that shape the architecture and prevalence of complex diseases.},
  author       = {Berg, Jeremy J. and Li, Xinyi and Riall, Kellen and Hayward, Laura and Sella, Guy},
  issn         = {1943-2631},
  journal      = {Genetics},
  number       = {4},
  publisher    = {Oxford University Press},
  title        = {{Mutation–selection–drift balance models of complex diseases}},
  doi          = {10.1093/genetics/iyaf220},
  volume       = {231},
  year         = {2025},
}

@article{20330,
  abstract     = {The evolution of sexual dimorphism (the difference in average trait values between females and males, SD), is often thought to be constrained by shared genetic architecture between the sexes. Indeed, it is commonly expected that SD should negatively correlate with the intersex correlation (the genetic correlation between effects of segregating variants in females and males, r fm), either because (1) traits with ancestrally low r fm are less constrained in their ability to respond to sex-specific selection and thus evolve to be more dimorphic, or because (2) sex-specific selection, driving sexual dimorphism evolution, also acts to reduce r fm. Despite the intuitive appeal and prominence of these ideas, their generality and the conditions in which they hold remain unclear. Here, we develop models incorporating sex-specific stabilizing selection, mutation and genetic drift to examine the relationship between r fm and SD. We show that the two commonly-discussed mechanisms with the potential to generate a negative correlation between SD and r fm could just as easily generate a positive association, since the standard line of reasoning hinges on a hidden assumption that sex-specific adaptation more frequently favors increased dimorphism than reduced dimorphism. Our results provide, to our knowledge, the first mechanistic framework for understanding the conditions under which a correlation between r fm and SD may arise and offer a compelling explanation for inconsistent empirical evidence. We also make the intriguing observation that—even when selection between the two sexes is identical—drift generates nonzero SD. We quantify this effect and discuss its significance.},
  author       = {Puixeu Sala, Gemma and Hayward, Laura},
  issn         = {1943-2631},
  journal      = {Genetics},
  number       = {3},
  publisher    = {Oxford University Press},
  title        = {{The relationship between sexual dimorphism and intersex correlation: Do models support intuition?}},
  doi          = {10.1093/genetics/iyaf175},
  volume       = {231},
  year         = {2025},
}

@article{12157,
  abstract     = {Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.},
  author       = {Hayward, Laura and Sella, Guy},
  issn         = {2050-084X},
  journal      = {eLife},
  keywords     = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
  publisher    = {eLife Sciences Publications},
  title        = {{Polygenic adaptation after a sudden change in environment}},
  doi          = {10.7554/elife.66697},
  volume       = {11},
  year         = {2022},
}