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.

Various aspects of brain organization differ between the left and right hemispheres. Clues to the developmental origins of these asymmetries may be gained through associations with situs inversus totalis (SIT), a rare condition in which visceral organs are reversed on the left-right axis. In the largest previous brain imaging analyses of SIT (38 cases, 38 controls from Belgium), typical functional asymmetries such as left-hemisphere language dominance were mostly unaltered, but various aspects of asymmetrical cerebral structure - petalia, bending, and posterior venous anatomy - were often reversed in this condition. SIT can be a monogenic trait that arises from rare genetic variants, usually affecting motile cilia which help to create the embryonic left-right body axis. However, most SIT cases do not have obvious genetic causes and may arise from environmental or random effects during embryogenesis. We sequenced the genomes of 23 SIT cases and 23 controls from the Belgian brain imaging dataset and pooled with prior data from 15 cases and 15 controls. We aimed to discover whether there are altered brain asymmetries in SIT cases with disruptive DNA variants in ciliary genes, or in other types of genes, as compared to genetically unsolved cases. In total, 19 cases had likely causal variants affecting ciliary function, while 19 cases remained genetically unsolved. Functional and structural brain asymmetries were not significantly different in genetically solved versus unsolved SIT cases. Therefore, functional brain asymmetries seem largely independent of known mechanisms of visceral situs formation, while structural brain torque is altered in SIT regardless of the presence or absence of overt genetic causes.

The ability to read is an important life skill and a major route to education. Dyslexia, characterized by difficulties with accurate/ fluent word reading, and poor spelling is influenced by genetic variation, with a twin study heritability estimate of 0.4–0.6. Until recently, genomic investigations were limited by modest sample size. We used a multivariate genome-wide association study (GWAS) method, MTAG, to leverage summary statistics from two independent GWAS efforts, boosting power for analyses of dyslexia; the GenLang meta-analysis of word reading (N = 27,180) and the 23andMe, Inc., study of dyslexia (Ncases = 51,800, Ncontrols = 1,087,070). We increased the effective sample size to 1,228,832 participants, representing the largest genetic study of reading-related phenotypes to date. Our analyses identified 80 independent genome-wide significant loci, including 36 regions which were not previously reported as significant. Of these 36 loci, 13 were novel regions with no prior association with dyslexia. We observed clear genetic correlations with cognitive and educational measures. Gene-set analyses revealed significant enrichment of dyslexia-associated genes in four neuronal biological process pathways, and findings were further supported by enrichment of neuronally expressed genes in the developing embryonic brain. Polygenic index analysis of our multivariate results predicted between 2.34–4.73% of variance in reading traits in an independent sample, the National Child Development Study cohort (N = 6410). Polygenic adaptation was examined using a large panel of ancient genomes spanning the last ~15 k years. We did not find evidence of selection, suggesting that dyslexia has not been subject to recent selection pressure in Europeans. By combining existing datasets to improve statistical power, these results provide novel insights into the biology of dyslexia.

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.

Impaired musical rhythm abilities and developmental speech-language related disorders are biologically and clinically intertwined. Prior work examining their relationship has primarily used small samples; here, we studied associations at population-scale by conducting the largest systematic epidemiological investigation to date (total N = 39,092). Based on existing theoretical frameworks, we predicted that rhythm impairment would be a significant risk factor for speech-language disorders in the general adult population. Findings were consistent across multiple independent datasets and rhythm subskills (including beat synchronization and rhythm discrimination), and aggregate meta-analyzed data showed that rhythm impairment is a modest but consistent risk factor for developmental speech, language, and reading disorders (OR = 1.32 [1.14 – 1.49]; p < .0001). Further, cross-trait polygenic score analyses indicate shared genetic architecture between musical rhythm and reading abilities, providing evidence for genetic pleiotropy between rhythm and language-related phenotypes.

Developmental stuttering is a common childhood condition characterized by disfluencies in speech, such as blocks, prolongations, and repetitions. While most children who stutter do so only transiently, there are some for whom stuttering persists into adulthood. Rare-variant screens in families including multiple relatives with persistent stuttering have so far identified six genes carrying putative pathogenic variants hypothesized to act in a monogenic fashion. Here, we applied a complementary study design, searching instead for de novo variants in exomes of 85 independent parent-child trios, each with a child with transient or persistent stuttering. Exome sequencing analysis yielded a pathogenic variant in SPTBN1 as well as likely pathogenic variants in PRPF8, TRIO, and ZBTB7A - four genes previously implicated in neurodevelopmental disorders with or without speech problems. Our results also highlighted two further genes of interest for stuttering: FLT3 and IREB2. We used extensive bioinformatic approaches to investigate overlaps in brain-related processes among the twelve genes associated with monogenic forms of stuttering. Analyses of gene-expression datasets of the developing and adult human brain, and data from a genome-wide association study of human brain structural connectivity, did not find links of monogenic stuttering to specific brain processes. Overall, our results provide the first direct genetic link between stuttering and other neurodevelopmental disorders, including speech delay and aphasia. In addition, we systematically demonstrate a dissimilarity in biological pathways associated with the genes thus far implicated in monogenic forms of stuttering, indicating heterogeneity in the etiological basis of this condition.

Advances in paleogenetics allowed the identification of protein-coding changes unique to Homo sapiens by comparing present-day and archaic hominin genomes. So far, experimental validation has been restricted to functional assays and model organisms. Large-scale biobanking now makes it possible to directly assess phenotypic consequences in living adults. Querying exomes of 455,000 UK Biobank participants at 37 sites with supposedly fixed human-specific changes, we identified 103 carriers at 17 positions, with variable allele counts across ancestries. We performed phenotypic evaluations for two example changes. Individuals carrying archaic SSH2 alleles showed no clear deviations in an array of health, neuropsychiatric, and cognitive traits. Carriers of a TKTL1 missense variant, previously linked to large effects on cortical neurogenesis, showed no obvious differences in brain anatomy, with many carriers holding college degrees. Our study demonstrates challenges associated with individual interrogation of key sites when seeking insights into the evolution of complex human traits and highlights the importance of including diverse ancestries in biobanking efforts.

Social behaviour is a heritable, context-dependent trait that changes across social settings and development, influencing wellbeing and mental health. We present the first genome-wide meta-regression study of social behaviour from infancy to early adulthood, leveraging 491,246 repeat measures of low prosocial behaviour and peer/social difficulties in European-ancestry cohorts (Neff=121,777, Nind=73,321). We modelled heterogeneity in genetic effects across social domains, informants, and ages (2–29 years), capturing social context through genomic influences. Six loci were identified, including variation within CADM2 ( p =2.51x10-[9][1]). The SNP-based heritability was modest (2–7%), and the genetic architecture of social behaviour multidimensional. Polygenic scores demonstrated predictability and accuracy in independent European-ancestry cohorts and, partially, in African-ancestry cohorts (Nind=16,305). Genetic correlations with later-life and mental health outcomes showed context-dependent patterns. Modelling predicted onsets of associations with social behaviour revealed distinct profiles, as observed for autism, ADHD, depression and schizophrenia, highlighting novel opportunities to genetically proxy developmental trajectories. ### Competing Interest Statement H.L. reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; all outside the submitted work. H.L. is editor-in-chief of JCPP Advances. J.A.R-Q. was on the speakers bureau and/or acted as a consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubio, Uriach, Technofarma and Raffo in the last 3 years. J.A.R-Q. also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubio, Takeda, Bial and Medice. The Department of Psychiatry, chaired by J.A.R-Q., received unrestricted educational and research support from the following companies in the last 3 years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubio. E.D.R. has served as a speaker for Shire Sweden AB, a Takeda Pharmaceutical Company, outside of this work. S.B. discloses that he has in the last 3 years acted as a consultant or lecturer for Medice, Takeda, and LinusBio. S.B. receives royalties for textbooks and diagnostic tools from Hogrefe, UTB, Ernst Reinhardt, Kohlhammer, and Liber. S.B. is a partner in NeuroSupportSolutions International AB. All other authors declare no conflict of interest. R2D2-MH, Horizon Europe, 101057385 R2D2-MH, UK Research and Innovation (UKRI), under the UK government’s Horizon Europe funding guarantee, 10039383 R2D2-MH, Swiss State Secretariat for Education, Research and Innovation (SERI), contract number: 22.00277 ZonMW, TOP 40–00812–98–11010 Horizon Europe Research and Innovation Programme, FAMILY, 101057529, HappyMums, 101057390 European Research Council, TEMPO, 101039672 Dutch Ministry of Education, Culture, and Science and the Netherlands Organisation for Scientific Research, 024.001.003, Consortium on Individual Development, NWO-VICI, NWO-ZonMW: 016.VICI.170.200 Horizon 2020 research and innovation program, Contract grant no. 633595, DynaHealth, LongITools, 874739, EarlyCause, 848158 China Scholarship Council, 201706990036 Max Planck Society Radboud University Donders RSF 2025 Ter Meulen Grant of the Royal Netherlands Academy of Arts and Sciences (KNAW) Strategic Research Council (SRC) established within the Academy of Finland, decision no. 352700 Instituto de Salud Carlos III, co-funded by the European Union Fund (Fondo Social Europeo Plus, FSE+), contract no. CP22/00026 Research Council of Norway (RCN), #274611, #336085, #274611, #274611, #288083, #336078 South-Eastern Norway Regional Health Authority (HSO), #2020022, #2018059, #2021045 MRC Integrative Epidemiology Unit, University of Bristol, Medical Research Council, University of Bristol, MC\_UU\_00032/1 European Union, 101045526, 818425 University of Oulu, Academy of Finland Profi6, decision number AF 336449 Research Council of Finland, STAGE [Grant N° 101137146], IHEN [Grant N° 101137317], OBELISK Grant [N° 101080465], OBCT [Grant N° 101080250], TRIGGER [Grant N° 101057739] Research Council of Finland, 356888 MRC Centre for Environment and Health, Medical Research Council, UK, MR/S019669/1 Simons Foundation, 724306 Sir Henry Wellcome Postdoctoral Fellowship, 213514/Z/18/Z Ministry of Science, Technology and Innovation, https://ror.org/012s3r374, State Research Agency grant RYC2022-038136-I, European Union FSE+, State Research Agency grant PID2022-143106OA-I00, European Union FEDER William H. Gates Sr. Fellowship from the Alzheimer’s Disease Data Initiative UK Medical Research Council, Grant Nos. MR/V012878/1 and previously MR/M021475/1 US National Institutes of Health, AG046938 European Research Council under the European Union's Seventh Framework Programme, FP7/2007-2013, grant agreement n° 602768 UK Research and Innovation, 10063472 EU-AIMS (European Autism Interventions) & AIMS-2-TRIALS, European Union FP7 & Horizon2020 Programmes, the European Federation of Pharmaceutical Industries and Associations (EFPIA), AUTISM SPEAKS, Autistica, SFARI,, Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, Horizon2020 supported programme CANDY Grant No. 847818 [1]: #ref-9

Genetic investigations of people with speech and language disorders can provide windows into key aspects of human biology. Most genomic research into impaired speech development has so far focused on childhood apraxia of speech (CAS), a rare neurodevelopmental disorder characterized by difficulties with coordinating rapid fine motor sequences that underlie proficient speech. In 2001, pathogenic variants of FOXP2 provided the first molecular genetic accounts of CAS aetiology. Since then, disruptions in several other genes have been implicated in CAS, with a substantial proportion of cases being explained by high-penetrance variants. However, the genetic architecture underlying other speech-related disorders remains less well understood. Thus, in the present study, we used systematic DNA sequencing methods to investigate idiopathic speech delay, as characterized by delayed speech development in the absence of a motor speech diagnosis (such as CAS), a language/reading disorder, or intellectual disability. We performed genome sequencing in a cohort of 23 children with a rigorous diagnosis of idiopathic speech delay. For roughly half of the sample (ten probands), sufficient DNA was also available for genome sequencing in both parents, allowing discovery of de novo variants. In the thirteen singleton probands, we focused on identifying loss-of-function and likely damaging missense variants in genes intolerant to such mutations. We found that one speech delay proband carried a pathogenic frameshift deletion in SETD1A, a gene previously implicated in a broader variable monogenic syndrome characterized by global developmental problems including delayed speech and/or language development, mild intellectual disability, facial dysmorphisms, and behavioural and psychiatric symptoms. Of note, pathogenic SETD1A variants have been independently reported in children with CAS in two separate studies. In other probands in our speech delay cohort, likely pathogenic missense variants were identified affecting highly conserved amino acids in key functional domains of SPTBN1 and ARF3. Overall, this study expands the phenotype spectrum associated with pathogenic SETD1A variants, to also include idiopathic speech delay without CAS or intellectual disability, and suggests additional novel potential candidate genes that may harbour high-penetrance variants that can disrupt speech development.

Purpose: Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life. Method: The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden. Results: We identified a high- ( n = 230) and a low-burden subgroup ( n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden. Conclusions: Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering. Supplemental Material: https://doi.org/10.23641/asha.25582980

Compared with our fossil ancestors and Neandertal kin, modern humans have evolved a distinctive skull shape, with a rounder braincase and more delicate face. Competing explanations for this rounder skull have either linked it to changes in brain organisation, or seen it as a by-product of gracilization (evolution of thinner and lighter skeletal anatomy). Here, we combined palaeoanthropological data from hominin fossils and imaging genomics data from living humans to gain insight into evolutionary and developmental mechanisms shaping this uniquely modern human phenotype. We analysed endocranial globularity from magnetic resonance imaging (MRI) brain scans and genetic data of more than 33,000 adults. We discovered 28 genomic loci significantly associated with endocranial globularity. There was genetic overlap with the brain’s ventricular system, white matter microstructure, and sulcal morphology, and with multivariate genetic analyses of reading/language skills, but not with general cognition. The associated genes exhibited enriched expression in the brain during prenatal development and early childhood. The connection to the ventricular system hints at a role for cerebrospinal fluid pressure in shaping the endocranium during development. Genes linked to endocranial globularity also showed enhanced expression in the cardiovascular and female reproductive systems. This finding suggests co-evolutionary pathways whereby changes impacting factors such as energy needs, pregnancy, or fertility concurrently shape the brain and its structure.### Competing Interest StatementThe authors have declared no competing interest.

Background From listening to playing music or singing in a group, social engagement with music can be a highly rewarding activity (e.g., Cross et al. 2001). Past studies have reported positive effects of group music activities on mental health and wellbeing, ranging from improved quality of life and social resilience, to reduced depression (e.g., Deatrich et al. 2016; Fancourt et al. 2016). Previous results show that individual differences in sensitivity to reward from social aspects of music are heritable (twin-based heritability h2twin = .52; Bignardi et al., 2024) and display strong genetic correlations with objectively assessed music perceptual abilities. Yet, how reward from social bonding through music genetically relates to mental and psychiatric traits remains unclear. Here, we attempt to: (1) better characterize genetic influences on liking to sing or play music with other people, using a combination of multivariate twin-modelling and genome-wide approaches; and (2) assess how genetic predisposition for mental and personality traits relate to enjoyment of group music activities. Methods Applying a multivariate twin-modelling approach, we selected the best candidate item capturing aspects of reward from social bonding through music. First, we analysed items from the social reward facets of the Barcelona Music Reward Questionnaire (BMRQ; Mas-Herrero et al. 2012) in a Swedish Sample (STAGE, N = 9,169). Based on h2twin estimates, we selected the BMRQ item 13, “I like to sing or play an instrument with other people”, and jointly estimated SNP-based (h2SNP) and family-based heritability (h2total) in a Dutch sample of partly related individuals (Lifelines, N = 15,645) using a Genome-based restricted maximum likelihood with multiple genetic relatedness matrices. To understand how social bonding in the musical context genetically relates to health, we will assess its relationship with polygenic risk scores (PGS) derived from selected psychiatric (i.e., generalized anxiety, major depressive, attention deficit/hyperactivity, autism spectrum, bipolar and post-traumatic stress disorder, suicidal ideation) and personality (i.e., neuroticism) traits. Results The twin-modelling approach in STAGE revealed a substantially higher h2twin for item 13 (h2twin = .55, 95% CI [.51, .58]), as compared to other BMRQ “Social Reward” items. In addition, a large component of item 13 h2twin was found to be item-specific (h2twin = .41, 95% CI [.37, .45]), i.e., not shared with the other items used to assess “Social Reward”. Analysis in Lifeline on the same trait revealed h2SNP estimates of 0.12 (SE = 0.02) with h2total of 0.43 (SE=0.03). Discussion Analyses confirm the heritable nature of social music enjoyment, aligning with previously reported estimates. The substantial component of genetic variation that is both unique and shared in item 13 might reflect interactions with other facets of cognition, including dispositions of the mind that can facilitate or hamper engagement in group music activities through modulation of reward perception. To explore the connections between mental/personality traits and this measure of group music enjoyment, we will assess genetic influences on neuropsychiatric and personality traits shape one's enjoyment of social music activities. With this, we hope to shed light on (1) whether social music enjoyment remains biologically conditioned by mental disposition and (2) the benefits of interindividual differences in social music playing.

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.

Recent advances in paleo-genetics allowed the identification of protein-coding changes apparently fixed on the lineage leading to Homo sapiens , by comparing genomes of present-day humans and archaic hominins. Although such genomic differences are thought to make key contributions to distinctly modern human traits, experimental validation of their potential impact was so far restricted to functional assays and model organisms. With the availability of large-scale genetically informative population databases, it now becomes possible to identify present-day carriers of rare archaic alleles of interest and to directly assess putative phenotypic consequences in living humans. We queried exome sequencing data of around half a million people in the UK Biobank in search of carriers of archaic alleles at 37 genomic positions with supposedly fixed human-specific changes. This search yielded 103 carriers of the archaic allele for 17 positions, with diverging allele counts across ancestries. We contrasted carriers of an exemplary archaic allele in SSH2 with a curated set of non-carriers, observing no deviation from the norm in a range of health, psychological, and cognitive traits. We also identified 62 carriers of the archaic allele of a missense change in the TKTL1 gene, previously reported to have large effects on cortical neurogenesis based on functional analyses in brain organoids and animal models. However, human carriers of the archaic TKTL1 allele did not show differences in anatomical brain measures and qualification level, compared to non-carriers. These results highlight the importance of investigating diverse ancestral populations for a more accurate representation of shared human variation and challenge the notion of permanently fixed genetic changes that set Homo sapiens apart from Neandertals and Denisovans. Lastly, we propose that future investigations should assess effects of multiple archaic alleles in aggregate, since any single genetic change is unlikely to itself explain the emergence of complex human traits. ### Competing Interest Statement The authors have declared no competing interest.

Background The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors, although mechanisms are not well understood. Here, we performed a meta-genome-wide association study within the EAGLE consortium and investigated polygenic overlap with later-life traits, including Attention-Deficit/Hyperactivity Disorder (ADHD) and cognition. Methods We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months) and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated Single-Nucleotide Polymorphism heritability (SNP-h 2 ), genetic correlations (r g ) and modelled underlying genetic factor structures with multivariate models. Results Contributions of common genetic variation to early-life vocabulary were modest (SNP-h 2 : 0.08(SE=0.01) to 0.24(SE=0.03)) and multi-factorial. Genetic overlap between infant expressive and toddler receptive vocabulary was near zero (r g =0.07(SE=0.10)), although both measures were genetically related to toddler expressive vocabulary (r g =0.69(SE=0.14) and r g =0.67(SE=0.16), respectively). Consistently, polygenic association patterns with later-life traits differed: Genetic links with cognition emerged only in toddlerhood (e.g. toddler receptive vocabulary and intelligence: r g =0.36(SE=0.12)), despite comparable study power for infant measures. Furthermore, increased polygenic ADHD risk was associated with larger infant expressive vocabulary (r g =0.23(SE=0.08)), as confirmed by ADHD-symptom-based follow-up analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC-r g =0.54(SE=0.26)). Genetic relationships with toddler receptive vocabulary were, however, opposite (ALSPAC-r g =-0.74(SE=0.23)), highlighting developmental changes in genetic architectures. Conclusions Multiple genetic components contribute to early-life vocabulary development, shaping polygenic association patterns with later-life ADHD symptoms and cognition.