Saint Pierre, A. | Search bioRxiv

bioRxiv2023

A model for co-occurrent assortative mating and vertical cultural transmission and its impact on measures of genetic associations

Assortative mating for a given phenotype is the phenomenon by which mates select each other based on their phenotypic similarity. Other phenomena can create positive correlation between the parents and the offsprings environment: vertical cultural transmission, or dynastic effects. When these phenomena occur together, they induce a gene-environment correlation at the population scale. It will impact genetic measures of associations such as SNP effect size and SNP-heritability. In this paper, we provide a complete mathematical modelling of both assortative mating and vertical cultural transmission in the classical framework of the polygenic additive model. We establish for the first time the theoretical evolution and equilibrium values of all quantities of interest involved. We then derive its consequences on typical genetic epidemiology analyses; including both population and family-based study designs. We show the consequences on heritability estimation, Genome-Wide Association Studies (GWAS), and the variance explained by polygenic scores. We validate our calculations through simple forward-time simulations.

genetics↗

bioRxiv2022

Genetic population structure across Brittany and the downstream Loire basin provides new insights on the demographic history of Western Europe

European genetic ancestry originates from three main ancestral populations - Western hunter-gatherers, early European farmers and Yamnaya Eurasian herders - whose edges geographically met in present-day France. Despite its central role to our understanding of how the ancestral populations interacted and gave rise to modern population structure, the population history of France has remained largely understudied. Here, we analysed the high-coverage whole-genome sequences and genome-wide genotype profiles of respectively 856 and 3,234 present-day individuals from the northern half of France, and merged them with publicly available present-day and ancient Europe-wide genotype datasets. We also explored, for the first time, the whole-genome sequences of six mediaeval individuals (300-1100 CE) from Western France to gain insights into the genetic impact of what is commonly known as the Migration Period in Europe. We found extensive fine-scale population structure across Brittany and the downstream Loire basin, emphasising the need for investigating local populations to better understand the distribution of rare and putatively deleterious variants across space. Overall, we observed an increased population differentiation between the northern and southern sides of the river Loire, which are characterised by different proportions of steppe vs. Neolithic-related ancestry. Samples from Western Brittany carry the largest levels of steppe ancestry and show high levels of allele sharing with individuals associated with the Bell Beaker complex, levels that are only comparable with those found in populations lying on the northwestern edges of Europe. Together, our results imply that present-day individuals from Western Brittany retain substantial legacy of the genetic changes that occurred in Northwestern Europe following the arrival of the Bell Beaker people c. 2500 BCE. Such genetic legacy may explain the sharing of disease-related alleles with other present-day populations from Western Britain and Ireland.

genetics↗