Biology subjects

St. Pourcain, B.

Publications and source records attributed to St. Pourcain, B..

3 recordsLinked to original sources

bioRxiv2022

Genomic contributions to infant and toddler vocabulary scores: Implications for association with health-, cognition- and behaviour-related outcomes

BackgroundThe 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. MethodsWe 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-h2), genetic correlations (rg) and modelled underlying genetic factor structures with multivariate models. ResultsContributions of common genetic variation to early-life vocabulary were modest (SNP-h2: 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 (rg=0.07(SE=0.10)), although both measures were genetically related to toddler expressive vocabulary (rg=0.69(SE=0.14) and rg=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: rg=0.36(SE=0.12)), despite comparable study power for infant measures. Furthermore, increased polygenic ADHD risk was associated with larger infant expressive vocabulary (rg=0.23(SE=0.08)), as confirmed by ADHD-symptom-based follow-up analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC-rg=0.54(SE=0.26)). Genetic relationships with toddler receptive vocabulary were, however, opposite (ALSPAC-rg=-0.74(SE=0.23)), highlighting developmental changes in genetic architectures. ConclusionsMultiple genetic components contribute to early-life vocabulary development, shaping polygenic association patterns with later-life ADHD symptoms and cognition.

genomics↗

bioRxiv2018

Alcohol consumption and mate choice in UK Biobank: comparing observational and Mendelian randomization estimates

Alcohol use is correlated within spouse-pairs, but it is difficult to disentangle the effects of alcohol consumption on mate-selection from social factors or cohabitation leading to spouses becoming more similar over time. We hypothesised that genetic variants related to alcohol consumption may, via their effect on alcohol behaviour, influence mate selection. Therefore, in a sample of over 47,000 spouse-pairs in the UK Biobank we utilised a well-characterised alcohol related variant, rs1229984 in ADH1B, as a genetic proxy for alcohol use. We compared the phenotypic concordance between spouses for self-reported alcohol use with the association between an individuals self-reported alcohol use and their partners rs1229984 genotype using Mendelian randomization. This was followed up by an exploration of the spousal genotypic concordance for the variant and an analysis determining if relationship length may be related to spousal alcohol behaviour similarities. We found strong evidence that both an individuals self-reported alcohol consumption and rs1229984 genotype are associated with their partners self-reported alcohol use. The Mendelian randomization analysis found that each unit increase in an individuals weekly alcohol consumption increased their partners alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P=1.10x10-5). Furthermore, the rs1229984 genotype was concordant within spouse-pairs, suggesting that some spousal concordance for alcohol consumption existed prior to cohabitation. Although the SNP is strongly associated with ancestry, our results suggest that this concordance is unlikely to be explained by population stratification. Overall, our findings suggest that alcohol behaviour directly influences mate selection.

genetics↗

bioRxiv2017

Developmental changes within the genetic architecture of social communication behaviour: A multivariate study of genetic variance in unrelated individuals

BackgroundRecent analyses of trait-disorder overlap suggest that psychiatric dimensions may relate to distinct sets of genes that exert their maximum influence during different periods of development. This includes analyses of social-communciation difficulties that share, depending on their developmental stage, stronger genetic links with either Autism Spectrum Disorder or schizophrenia. Here we developed a multivariate analysis framework in unrelated individuals to model directly the developmental profile of genetic influences contributing to complex traits, such as social-communication difficulties, during a [~]10-year period spanning childhood and adolescence.\n\nMethodsLongitudinally assessed quantitative social-communication problems (N[≤] 5,551) were studied in participants from a UK birth cohort (ALSPAC, 8 to 17 years). Using standardised measures, genetic architectures were investigated with novel multivariate genetic-relationship-matrix structural equation models (GSEM) incorporating whole-genome genotyping information. Analogous to twin research, GSEM included Cholesky decomposition, common pathway and independent pathway models.\n\nResultsA 2-factor Cholesky decomposition model described the data best. One genetic factor was common to SCDC measures across development, the other accounted for independent variation at 11 years and later, consistent with distinct developmental profiles in trait-disorder overlap. Importantly, genetic factors operating at 8 years explained only [~]50% of the genetic variation at 17 years.\n\nConclusionUsing latent factor models, we identified developmental changes in the genetic architecture of social-communication difficulties that enhance the understanding of ASD and schizophrenia-related dimensions. More generally, GSEM present a framework for modelling shared genetic aetiologies between phenotypes and can provide prior information with respect to patterns and continuity of trait-disorder overlap.

genetics↗