Publications

Abstract

Art can evoke strong emotional responses in humans. Here, we examine genetic contributions to chills, a marker of such responses. We gather self-reports from a genotyped sample of thousands of partly related individuals from the Netherlands (n = 15,606). Using genomic relationships based on common single-nucleotide polymorphism (SNP) data, we find that up to 29% of the variation in proneness to aesthetic (visual art and poetry) and music chills can be explained by familial relatedness effects, one-fourth of which is attributed to SNP variation. Furthermore, we reveal a moderate genetic correlation of .58 between aesthetic and music chills, pointing to shared genetic variation affecting susceptibility to strong emotional responses across different art forms. Finally, we find that a polygenic index (PGI) for openness to experience (n = 220,015) is associated with susceptibilities to both aesthetic and music chills. Our results show that additive genetic variation, but also familial relatedness beyond shared common SNPs, contributes to proneness to chills from artistic, poetic, and musical expressions. These results open up a promising path towards studying the human attitude towards art, via both state-of-the-art genomics and intergenerational models of transmission.

Abstract

Social behaviour is a heritable trait linked to well-being and mental health, yet it varies across social context, including social domains, informants and development, which may shape its underlying genomic architecture. Here, we conducted a genome-wide meta-regression meta-analysis of social behaviour from infancy to early adulthood, studying ~500,000 repeated measures in European-ancestry cohorts (N = 73,321). We modelled heterogeneity in single-variant associations across social domains (low prosocial behaviour and peer/social difficulties), multiple informants (parents, teachers and self-reports) and ages (2–29 years), identifying 6 associated loci, including variation within CADM2 (P = 2.51 × 10−9). Single nucleotide polymorphism-based heritability ranged from 2% to 7%, and the genetic architecture comprised 4 factors reflecting differences in either social domains or informants. Polygenic scores (N = 16,305) accurately predicted contextual variation in independent cohorts, with some cross-ancestry transferability. Context-specific patterns of genetic correlations, particularly when estimating the developmental onset of associations, offer opportunities to disentangle shared trajectories linking social behaviour with later-life and mental health outcomes.

Abstract

Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of polycomb repressive complex 2 (PRC2)-associated H3K27me3 in the chromatin of naive pluripotent stem cells and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, whereas inhibition of PRC2 promotes trophoblast-fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.