Publications

Abstract

Rhythm and language-related traits are phenotypically correlated, but their genetic overlap is largely unknown. Here, we leveraged two large-scale genome-wide association studies performed to shed light on the shared genetics of rhythm (N=606,825) and dyslexia (N=1,138,870). Our results reveal an intricate shared genetic and neurobiological architecture, and lay groundwork for resolving longstanding debates about the potential co-evolution of human language and musical traits.

Abstract

Humans engage with music for various reasons that range from emotional regulation and relaxation to social bonding. While there are large inter-individual differences in how much humans enjoy music, little is known about the origins of those differences. Here, we disentangle the genetic factors underlying such variation. We collect data on several facets of music reward sensitivity, as measured by the Barcelona Music Reward Questionnaire, plus music perceptual abilities and general reward sensitivity from a large sample of Swedish twins (N = 9169; 2305 complete pairs). We estimate that genetic effects contribute up to 54% of the variability in music reward sensitivity, with 70% of these effects being independent of music perceptual abilities and general reward sensitivity. Furthermore, multivariate analyses show that genetic and environmental influences on the different facets of music reward sensitivity are partly distinct, uncovering distinct pathways to music enjoyment and different patterns of genetic associations with objectively assessed music perceptual abilities. These results paint a complex picture in which partially distinct sources of variation contribute to different aspects of musical enjoyment.

Abstract

Dyslexia is a learning difficulty with neurodevelopmental origins, manifesting as reduced accuracy and speed in reading and spelling. It is substantially heritable and frequently co-occurs with other neurodevelopmental conditions, particularly attention deficit-hyperactivity disorder (ADHD). Here, we investigate the genetic structure underlying dyslexia and a range of psychiatric traits using results from genome-wide association studies of dyslexia, ADHD, autism, anorexia nervosa, anxiety, bipolar disorder, major depressive disorder, obsessive compulsive disorder,
schizophrenia, and Tourette syndrome. Genomic Structural Equation Modelling (GenomicSEM) showed heightened support for a model consisting of five correlated latent genomic factors described as: F1) compulsive disorders (including obsessive-compulsive disorder, anorexia nervosa, Tourette syndrome), F2) psychotic disorder (including bipolar disorder, schizophrenia), F3) internalising disorders (including anxiety disorder, major depressive disorder), F4) neurodevelopmental traits (including autism, ADHD), and F5) attention and learning difficulties (including ADHD, dyslexia). ADHD loaded more strongly on the attention and learning difficulties latent factor (F5) than on the neurodevelopmental traits latent factor (F4). The attention and learning difficulties latent factor (F5) was positively correlated with internalising disorders (.40), neurodevelopmental traits (.25) and psychotic disorders (.17) latent factors, and negatively correlated with the compulsive disorders (–.16) latent factor. These factor correlations are mirrored in genetic correlations observed between the attention and learning difficulties latent factor and other cognitive, psychological and wellbeing traits. We further investigated genetic variants underlying both dyslexia and ADHD, which implicated 49 loci (40 not previously found in GWAS of the individual traits) mapping to 174 genes (121 not found in GWAS of individual traits) as potential pleiotropic variants. Our study confirms the increased genetic relation between dyslexia and ADHD versus other psychiatric traits and uncovers novel pleiotropic variants affecting both traits. In future, analyses including additional co-occurring traits such as dyscalculia and dyspraxia will allow a clearer definition of the attention and learning difficulties latent factor, yielding further insights into factor structure and pleiotropic effects.

Abstract

Lateralization is a defining characteristic of the human brain, often studied through localized approaches that focus on interhemispheric differences between homologous pairs of regions. It is also important to emphasize an integrative perspective of global brain asymmetry, in which hemispheric differences are understood through global patterns across the entire brain.

Abstract

Finding and facilitating commonalities between the linguistic behaviors of large language models and humans could lead to major breakthroughs in our understanding of the acquisition, processing, and evolution of language. However, most findings on human–LLM similarity can be attributed to training on human data. The field of emergent machine-to-machine communication provides an ideal testbed for discovering which pressures are neural agents naturally exposed to when learning to communicate in isolation, without any human language to start with. Here, we review three cases where mismatches between the emergent linguistic behavior of neural agents and humans were resolved thanks to introducing theoretically-motivated inductive biases. By contrasting humans, large language models, and emergent communication agents, we then identify key pressures at play for language learning and emergence: communicative success, production effort, learnability, and other psycho-/sociolinguistic factors. We discuss their implications and relevance to the field of language evolution and acquisition. By mapping out the necessary inductive biases that make agents' emergent languages more human-like, we not only shed light on the underlying principles of human cognition and communication, but also inform and improve the very use of these models as valuable scientific tools for studying language learning, processing, use, and representation more broadly.

Abstract

Background

Neurodevelopmental conditions are highly heritable. Recent studies have shown that genomic heritability estimates can be confounded by genetic effects mediated via the environment (indirect genetic effects). However, the relative importance of direct versus indirect genetic effects on early variability in traits related to neurodevelopmental conditions is unknown.

Methods

The sample included up to 24,692 parent-offspring trios from the Norwegian MoBa cohort. We use Trio-GCTA to estimate latent direct and indirect genetic effects on mother-reported neurodevelopmental traits at age of 3 years (restricted and repetitive behaviors and interests, inattention, hyperactivity, language, social, and motor development). Further, we investigate to what extent direct and indirect effects are attributable to common genetic variants associated with autism, ADHD, developmental dyslexia, educational attainment, and cognitive ability using polygenic scores (PGS) in regression modeling.

Results

We find evidence for contributions of direct and indirect latent common genetic effects to inattention (direct: explaining 4.8% of variance, indirect: 6.7%) hyperactivity (direct: 1.3%, indirect: 9.6%), and restricted and repetitive behaviors (direct: 0.8%, indirect: 7.3%). Direct effects best explained variation in social and communication, language, and motor development (5.1%–5.7%). Direct genetic effects on inattention were captured by PGS for ADHD, educational attainment, and cognitive ability, whereas direct genetic effects on language development were captured by cognitive ability, educational attainment, and autism PGS. Indirect genetic effects on neurodevelopmental traits were primarily captured by educational attainment and/or cognitive ability PGS.

Conclusions

Results were consistent with differential contributions to neurodevelopmental traits in early childhood from direct and indirect genetic effects. Indirect effects were particularly important for hyperactivity and restricted and repetitive behaviors and interests and may be linked to genetic variation associated with cognition and educational attainment. Our findings illustrate the importance of within-family methods for disentangling genetic processes that influence early neurodevelopmental traits, even when identifiable associations are small.

Abstract

Advanced diffusion magnetic resonance imaging (dMRI) allows one to probe and assess brain white matter (WM) organisation and microstructure in vivo. Various dMRI models with different theoretical and practical assumptions have been developed, representing partly overlapping characteristics of the underlying brain biology with potentially complementary value in the cognitive and clinical neurosciences. To which degree the different dMRI metrics relate to clinically relevant geno- and phenotypes is still debated. Hence, we investigate how tract-based and whole WM skeleton parameters from different dMRI approaches associate with clinically relevant and white matter-related phenotypes (sex, age, pulse pressure (PP), body-mass-index (BMI), brain asymmetry) and genetic markers in the UK Biobank (UKB, n=52,140) and the Adolescent Brain Cognitive Development (ABCD) Study (n=5,844). In general, none of the imaging approaches could explain all examined phenotypes, though the approaches were overall similar in explaining variability of the examined phenotypes. Nevertheless, particular diffusion parameters of the used dMRI approaches stood out in explaining some important phenotypes known to correlate with general human health outcomes. A multi-compartment Bayesian dMRI approach provided the strongest WM associations with age, and together with diffusion tensor imaging, the largest accuracy for sex-classifications. We find a similar pattern of metric and tract-dependent asymmetries across datasets, with stronger asymmetries in ABCD data. The magnitude of WM associations with polygenic scores as well as PP depended more on the sample, and likely age, than dMRI metrics. However, kurtosis was most indicative of BMI and potentially of bipolar disorder polygenic scores. We conclude that WM microstructure is differentially associated with clinically relevant pheno- and genotypes at different points in life.

Abstract

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order1. Infections in bats are largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 mammalian genomes that revealed that signatures of selection in immune genes are more prevalent in bats than in other mammalian orders. We found an excess of immune gene adaptations in the ancestral chiropteran branch and in many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, which is an antiviral gene contributing to hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes in rhinolophid and hipposiderid bats. Cellular infection experiments show species-specific antiviral differences and an essential role of protein conjugation in antiviral function of bat ISG15, separate from its role in secretion and inflammation in humans. Furthermore, in contrast to humans, ISG15 in most rhinolophid and hipposiderid bats has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms that contribute to viral tolerance and disease resistance in bats.

Abstract

Combining academics and athletics is challenging but important for the psychological and psychosocial development of those involved. However, little is known about how experiences in academics spill over and relate to athletics. Drawing on the enrichment mechanisms proposed by the Work-Home Resources model, we posit that study crafting behaviours are positively related to volatile personal resources, which, in turn, are related to higher athletic achievement. Via structural equation modelling, we examine a path model among 243 student-athletes, incorporating study crafting behaviours and personal resources (i.e., positive affect and study engagement), and self- and coach-rated athletic achievement measured two weeks later. Results show that optimising the academic environment by crafting challenging study demands relates positively to positive affect and study engagement. In turn, positive affect related positively to self-rated athletic achievement, whereas – unexpectedly – study engagement related negatively to coach-rated athletic achievement. Optimising the academic environment through cognitive crafting and crafting social study resources did not relate to athletic outcomes. We discuss how these findings offer new insights into the interplay between academics and athletics.

Abstract

Apolipoprotein E ε4 is a major genetic risk factor for Alzheimer’s disease, and some apolipoprotein E ε4 carriers show Alzheimer’s disease–related neuropathology many years before cognitive changes are apparent. Therefore, studying healthy apolipoprotein E genotyped individuals offers an opportunity to investigate the earliest changes in brain measures that may signal the presence of disease-related processes. For example, subtle changes in functional magnetic resonance imaging functional connectivity, particularly within the default mode network, have been described when comparing healthy ε4 carriers to ε3 carriers. Similarly, very mild impairments of episodic memory have also been documented in healthy apolipoprotein E ε4 carriers. Here, we use a naturalistic activity (movie watching), and a marker of episodic memory encoding (transient changes in functional magnetic resonance imaging activity and functional connectivity around so-called ‘event boundaries’), to investigate potential phenotype differences associated with the apolipoprotein E ε4 genotype in a large sample of healthy adults. Using Bayes factor analyses, we found strong evidence against existence of differences associated with apolipoprotein E allelic status. Similarly, we did not find apolipoprotein E-associated differences when we ran exploratory analyses examining: functional system segregation across the whole brain, and connectivity within the default mode network. We conclude that apolipoprotein E genotype has little or no effect on how ongoing experiences are processed in healthy adults. The mild phenotype differences observed in some studies may reflect early effects of Alzheimer’s disease–related pathology in apolipoprotein E ε4 carriers.

Abstract

Hemispheric brain asymmetry is a basic organizational principle of the human brain and has been implicated in various psychiatric conditions, including autism spectrum disorder. Brain asymmetry is not a uniquely human feature and is observed in other species such as the mouse. Yet, asymmetry patterns are generally nuanced, and substantial sample sizes are required to detect these patterns. In this pre-registered study, we use a mouse dataset from the Province of Ontario Neurodevelopmental Network, which comprises structural MRI data from over 2000 mice, including genetic models for autism spectrum disorder, to reveal the scope and magnitude of hemispheric asymmetry in the mouse. Our findings demonstrate the presence of robust hemispheric asymmetry in the mouse brain, such as larger right hemispheric volumes towards the anterior pole and larger left hemispheric volumes toward the posterior pole, opposite to what has been shown in humans. This suggests the existence of species-specific traits. Further clustering analysis identified distinct asymmetry patterns in autism spectrum disorder models, a phenomenon that is also seen in atypically developing participants. Our study shows potential for the use of mouse models in studying the biological bases of typical and atypical brain asymmetry but also warrants caution as asymmetry patterns seem to differ between humans and mice.

Abstract

Left-right asymmetry is an important aspect of human brain organization for functions including language and hand motor control, which can be altered in some psychiatric traits. The last five years have seen rapid advances in the identification of specific genes linked to variation in asymmetry of the human brain and/or handedness. These advances have been driven by a new generation of large-scale genome-wide association studies, carried out in samples ranging from roughly 16,000 to over 1.5 million participants. The implicated genes tend to be most active in the embryonic and fetal brain, consistent with early developmental patterning of brain asymmetry. Several of the genes encode components of microtubules, or other microtubule-associated proteins. Microtubules are key elements of the internal cellular skeleton (cytoskeleton). A major challenge remains to understand how these genes affect, or even induce, the brain’s left-right axis. Several of the implicated genes have also been associated with psychiatric or neurological disorders, and polygenic dispositions to autism and schizophrenia have been associated with structural brain asymmetry. Knowledge of developmental mechanisms that lead to hemispheric specialization may ultimately help to define etiologic subtypes of brain disorders.

Abstract

This study investigated a developmental cascade between prosocial and linguistic abilities in a large sample (N = 11,051) from the general youth population in the United Kingdom (50% female, 46% living in disadvantaged neighborhoods, 13% non-White). Cross-lagged panel models showed that verbal ability at age 3 predicted prosociality at age 7, which in turn predicted verbal ability at age 11. Latent growth models also showed that gains in prosociality between 3 and 5 years were associated with increased verbal ability between 5 and 11 years and vice versa. Theory of mind and social competence at age 5 mediated the association between early childhood prosociality and late childhood verbal ability. These results remained robust even after controlling for socioeconomic factors, maternal mental health, parenting microclimate in the home environment, and individual characteristics (sex, ethnicity, and special educational needs). The findings suggest that language skills could be boosted through mentalizing activities and prosocial behaviors.