Biology subjects

Corfield, E. C.

Publications and source records attributed to Corfield, E. C..

9 recordsLinked to original sources

bioRxiv2025

Genome-wide analysis of social behaviour in context: a meta-regression approach across social domains, reporters and developmental stages

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). 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.

genomics↗

bioRxiv2025

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS. We identify 1,257 lead genetic variants associated with personality, including 823 novel variants. Common genetic variants explain 4.8%-9.3% of the variance in each trait, and 10.5%-16.2% accounting for measurement unreliability. Genetic effects on personality are highly consistent across geography, reporter (self vs. close other), age group, and measurement instrument, and we find minimal spousal assortment for personality in recent history. In stark contrast to many other social and behavioral traits, within-family GWAS and polygenic index analyses indicate little to no shared environmental confounding in genetic associations with personality. Polygenic prediction, genetic correlation, and Mendelian randomization analyses indicate that personality genetics have widespread, potentially causal associations with a wide range of consequential behaviors and life outcomes. The genetic architecture of personality is robust and fundamental to being a human.

genomics↗

bioRxiv2025

Separating direct, indirect and parent-of-origin genetic effects in the human population

Here, we present a novel approach to estimate the degree to which the phenotypic effect of a DNA locus is attributable to four components: alleles in the child (direct genetic effects), alleles in the mother and the father (indirect genetic effects), or is dependent upon the parent from which it is inherited (parent-of-origin, PofO effects). Applying our model, JODIE, to 30,000 child-mother-father trios with phased DNA information from the Estonian Biobank (EstBB) and the Norwegian Mother, Father, Child Cohort (MoBa), we jointly estimate the phenotypic variance attributable to these four effects unbiased of assortative mating (AM) for height, body mass index (BMI) and childhood educational test score (EA). For all three traits, direct effects make the largest contribution to the genetic effect variance. But we find that parental indirect genetic effects make an equivalent combined contribution, and that there is a non-zero PofO effect variance for all traits. We calculate the heritability that would be obtained at the populationlevel in the absence of AM for common DNA loci, and show that the proportional contribution of direct effects to these heritability values can be calculated as 64.0% for EA in MoBa, 77.1% and 63.4% for height in MoBa and EstBB, and 81.2% and 88.0% for BMI in MoBa and EstBB. Additionally, using within-family genome-wide association testing, we identify 276 independently associated DNA regions that replicate across two additional biobanks, which all show a genotype-phenotype relationship that reflects an interplay of direct, indirect and PofO effects. Determining how direct, parental and PofO genetic effects combine across loci genome-wide to influence human phenotypic variation requires joint modeling of parental and child genotypes alongside the parental origin of loci and here, we make the first attempt to do this in the human population.

genetics↗

bioRxiv2025

Genetic basis of partner choice

Previous genetic studies of human assortative mating have primarily focused on searching for its genomic footprint but have revealed limited insights into its biological and social mechanisms. Combining insights from the economics of the marriage market with advanced tools in statistical genetics, we perform the first genome-wide association study (GWAS) on a latent index for partner choice. Using 206,617 individuals from four global cohorts, we uncover phenotypic characteristics and social processes underlying assortative mating. We identify a broadly robust genetic component of the partner choice index between sexes and several countries and identify its genetic correlates. We also provide solutions to reduce assortative mating-driven biases in genetic studies of complex traits by conditioning GWAS summary statistics on the genetic associations with the latent partner choice index.

genetics↗

bioRxiv2023

Genetic similarity between relatives provides evidence on the presence and history of assortative mating

Assortative mating - the non-random mating of individuals with similar traits - is known to increase trait-specific genetic variance and genetic similarity between relatives. However, empirical evidence is limited for many traits, and the implications hinge on whether assortative mating has started recently or many generations ago. Here we show theoretically and empirically that genetic similarity between relatives can provide evidence on the presence and history of assortative mating. First, we employed path analysis to understand how assortative mating affects genetic similarity between family members across generations, finding that similarity between distant relatives is more affected than close relatives. Next, we correlated polygenic indices of 47,135 co-parents from the Norwegian Mother, Father, and Child Cohort Study (MoBa) and found genetic evidence of assortative mating in nine out of sixteen examined traits. The same traits showed elevated similarity between relatives, especially distant relatives. Six of the nine traits, including educational attainment, showed greater genetic variance among offspring, which is inconsistent with stable assortative mating over many generations. These results suggest an ongoing increase in familial similarity for these traits. The implications of this research extend to genetic methodology and the understanding of social and economic disparities.

genetics↗

bioRxiv2022

The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: MoBaPsychGen pipeline v.1

BackgroundThe Norwegian Mother, Father, and Child Cohort Study (MoBa) is a population-based pregnancy cohort, which includes approximately 114,500 children, 95,200 mothers, and 75,200 fathers. Genotyping of MoBa has been conducted through multiple research projects, spanning several years; using varying selection criteria, genotyping arrays, and genotyping centres. MoBa contains numerous interrelated families, which necessitated the implementation of a family-based quality control (QC) pipeline that verifies and accounts for diverse types of relatedness. MethodsThe MoBaPsychGen pipeline, comprising pre-imputation QC, phasing, imputation, and post-imputation QC, was developed based on current best-practice protocols and implemented to account for the complex structure of the MoBa genotype data. The pipeline includes QC on both single nucleotide polymorphism (SNP) and individual level. Phasing and imputation were performed using the publicly available Haplotype Reference Consortium release 1.1 panel as a reference. Information from the Medical Birth Registry of Norway and MoBa questionnaires were used to identify biological sex, year of birth, reported parent-offspring (PO) relationships, and multiple births (only available in the offspring generation). ResultsIn total, 207,569 unique individuals (90% of the unique individuals included in the study) and 6,981,748 autosomal SNPs passed the MoBaPsychGen pipeline. A further 174,462 chromosome X and 3,200 PAR SNPs are available in a subset of these individuals (N = 204,913 and 135,593, respectively). The relatedness checks performed throughout the pipeline allowed identification of within-generation and across-generation first-degree, second-degree, and third-degree relatives. The individuals passing post-imputation QC comprised 64,471 families ranging in size from singletons to 84 unique individuals (singletons are included as families as other family members may not have been genotyped, imputed, or passed post-imputation QC). The relationships identified include 287 monozygotic twin pairs, 22,884 full siblings, 117,004 PO pairs, 23,299 second-degree relative pairs, and 10,828 third-degree relative pairs. DiscussionMoBa contains a highly complex relatedness structure, with a variety of family structures including singletons, PO duos, full (mother, father, child) PO trios, nuclear families, blended families, and extended families. The availability of robustly quality-controlled genetic data for such a large cohort with a unique extended family structure will allow many novel research questions to be addressed. Furthermore, the MoBaPsychGen pipeline has potential utility in similar cohorts.

genetics↗

bioRxiv2019

Genome-wide Association Study of Pediatric Obsessive-Compulsive Traits: Shared Genetic Risk between Traits and Disorder

ObjectiveTo identify genetic variants associated with obsessive-compulsive (OC) traits and test for sharing of genetic risks between OC traits and obsessive-compulsive disorder (OCD). MethodsWe conducted a genome-wide association analysis of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of three OCD case-controls samples (cases=3384, controls=8363). Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. ResultsA locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase {delta}) was significantly associated with OC traits at the genome-wide significance level (p=2.48x10-8). The rs7856850 locus was also associated with OCD in a meta-analysis of three independent OCD case/control genome-wide datasets (p=0.0069). Polygenic risk scores derived from OC traits were significantly associated with OCD in a sample of childhood-onset OCD and vice versa (ps<0.01). OC traits were highly but not significantly genetically correlated with OCD (rg=0.83, p=0.07). ConclusionsWe report the first validated genome-wide significant variant for OC traits. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the importance of the type of measure used to measure traits as well as the feasibility and power of using trait-based approaches in community samples for genetic discovery.

genomics↗

bioRxiv2018

Utility of Attention-Deficit/Hyperactivity Disorder Trait Measure in Population Genetics: A Polygenic Risk Study

BackgroundValid and genetically-informative trait measures of psychopathology collected in the general population would provide a powerful complement to case/control genetic designs. We report the convergent, predictive and discriminant validity of the parent- and the self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN) for attention-deficit/hyperactivity disorder (ADHD) traits. We tested if SWAN ADHD scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as with traits and polygenic risk for co-occurring disorders such as anxiety and obsessive-compulsive disorder (OCD).\n\nMethodsWe collected parent- and self-report SWAN scores in a community sample (n=15,560; 6-18 years of age) and created norms. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with a community ADHD diagnosis (n=972) from those without a community diagnosis. We validated cut-points from the community sample in a clinical sample (266 ADHD cases; 36 controls). We tested if SWAN scores were associated with anxiety and obsessive-compulsive (OC) traits and polygenic risk for ADHD, OCD and anxiety disorders.\n\nResultsBoth the parent- and the self-report SWAN measures showed high convergent validity with established ADHD measures and distinguished ADHD participants with high sensitivity and specificity in the community sample. Cut-points established in the community sample discriminated ADHD clinic cases from controls with a sensitivity of 86% and specificity of 94%. High parent- and self-report SWAN scores and scores above the community-based cut-points were associated with polygenic risk for ADHD. High ADHD traits were associated with high anxiety traits, but not OC traits. SWAN scores were not associated with OCD or anxiety disorder polygenic risk.\n\nConclusionThe parent- and self-report SWAN are potentially useful in genetic research because they predict ADHD diagnoses and are associated with ADHD polygenic risk.

genetics↗

bioRxiv2018

Factor Structure and Heritability of Obsessive-Compulsive Traits in Children and Adolescents in the General Population

BackgroundObsessive-compulsive disorder (OCD) is a heritable childhood-onset psychiatric disorder that may represent the extreme of obsessive-compulsive (OC) traits that are widespread in the general population. We studied the factor structure and heritability of the Toronto Obsessive Compulsive Scale (TOCS), a new measure designed to assess traits associated with OCD in children and adolescents. We also examined the degree to which genetic effects are unique and shared between dimensions.\n\nMethodsOC traits were measured using the TOCS in 16,718 children and adolescents (6 to 18 years) at a local science museum. Factor analysis was conducted to identify OC trait dimensions. Univariate and multivariate twin modeling was performed to estimate the heritability of OC trait dimensions in a subset of twins (220 pairs).\n\nResultsSix OC dimensions were identified: Cleaning/Contamination, Hoarding, Rumination, Superstition, Counting/Checking, and Symmetry/Ordering. The TOCS total score (74%) and OC trait dimensions were heritable (30-77%). Hoarding was phenotypically distinct but shared genetic effects with other OC dimensions. Most of the genetic effects were shared between dimensions while unique environment accounted for the majority of dimension-specific variance, except for hoarding which had considerable unique genetic factors. A latent trait did not account for the shared variance between dimensions.\n\nConclusionsOC traits and individual OC dimensions were heritable, although the degree of shared and dimension-specific etiological factors varied by dimension. The TOCS is useful for genetic research of OC traits and OC dimensions should be examined individually and together along with total trait scores to characterize OC genetic architecture.

genetics↗