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Complex traits describe the majority of the range of anthropometric, disease, and behavioral variation in humans. Genome-wide association studies (GWAS) have been able to associate large regions of the genome to specific traits and diseases, explaining a fraction of their observed phenotypic variation. This ...

Complex traits describe the majority of the range of anthropometric, disease, and behavioral variation in humans. Genome-wide association studies (GWAS) have been able to associate large regions of the genome to specific traits and diseases, explaining a fraction of their observed phenotypic variation. This has led to the construction of polygenic predictors of complex traits for potential clinical applications and to their use in studies of polygenic selection. Recent studies and commentaries have called into question the generalizability of polygenic scores, the role of selection and our ability to robustly detect its impact on the evolution of complex traits, and the lack of diversity in association studies to accurately reflect present-day population heterogeneity. In light of this, new theoretical and empirical perspectives are needed to understand the role and interplay of ancestry, environment, population history, and natural selection in the evolution of complex traits. This is being manifested in the increased generation of both present-day and ancient DNA datasets from diverse human populations and in the development of statistical methods to investigate how the interaction between complex population histories, environment, and natural selection influences the genetic architecture and evolution of complex traits and diseases.

In this Research Topic, we want to highlight recent efforts to understand the genetic architecture and evolution of complex traits in diverse human populations. We also propose to include trans-disciplinary efforts that integrate genetics work with insights from the disciplines of history, anthropology, and archaeology. We are interested in thematic Review articles, empirical and theoretical methodological advances, simulation analyses, and analyses of present-day and/or ancient population genomics data.

These are sub-topics we would like to see addressed:
 • Genetic architecture of complex traits and diseases in diverse human populations
  o GWAS in trans-ethnic, structured, and admixed populations to parse shared and private genetic architectures
  o Improving association power for rare variants by analyzing diverse isolated populations, handling stratification in rare variant association studies
  o Considerations and limitations of polygenic trait scores
  o The contribution of common and rare variants to the heritability of complex traits in diverse populations
  o The role of gene regulation and methylation in complex trait variation
  o Multi-locus and multi-trait architectures: epistasis, pleiotropy, the omnigenic model
 • Evolution of complex traits and diseases in diverse human populations
  o Natural selection: the impact of negative, positive, and balancing selection on the evolution of complex traits
  o Spatial and temporal considerations
    The role of ancestry, population history and environment in complex trait variation
    Local adaptation, landscape genomics, and gene by environment interactions
    Temporal analyses of genetic and environmental data
  o Evolution of human cognition and the role of present-day disorders in human evolution
 • Historical and ethical considerations
  o Historical and epistemological analyses of genetic and anthropological studies of complex traits and lessons for present-day scientists
  o Considerations and ethics for sampling in diverse understudied populations

Keywords: complex traits, natural selection, GxE, evolutionary quantitative genetics, ancient DNA


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