Biology subjects

Ystrom, E.

Publications and source records attributed to Ystrom, E..

8 recordsLinked to original sources

bioRxiv2025

Longitudinal modelling reveals widespread non-additive genetic effects underlying developmental plasticity

Developmental plasticity, or the capacity of genotypes to produce different phenotypes under varying contexts, is poorly characterized in humans. Here we developed a longitudinal variance and a genotype-by-time model able to disentangle genetic effects from between-subject variability. Applied to early growth (infant length and BMI) and cognitive traits (math and reading) of 45,000 to 65,000 individuals, our models discovered 76 lead putative plasticity loci. Nearly all loci are novel; six replicate signals from independent interaction studies. We found evidence that additive genetic variation captures marginal effects from interactions, challenging the assumption that effect estimates from genome-wide association studies (GWAS) are purely additive. Notably, over 90% of putative plasticity loci are involved in distal intra-chromatin interactions implicating regulatory activity. Our findings provide molecular evidence that non-additive genetic variation contributes to complex traits and highlight the utility of longitudinal models in uncovering the biological underpinnings of trait plasticity.

genetics↗

bioRxiv2025

Parental Influence on Children's Educational Achievements: Analysing Direct and Indirect Genetic Effects through Trio-GCTA

Educational achievement is a key predictor of later-life outcomes, including financial security, social mobility, health, and mortality. Knowing its familial determinants, such as genetic predispositions, is crucial for understanding intergenerational educational mobility and addressing educational inequality. Here, we disentangle direct and indirect genetic effects on educational achievement using trio genome-wide complex trait analysis (Trio-GCTA). Leveraging up to 23,200 genotyped parent-offspring trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa), we find that direct genetic effects explain 15-21% of the variance in educational achievements, including 8th-grade national assessments in Math, Reading, and English, and 10th-grade grade point average (GPA). Notably, indirect genetic effects additionally explain 7-15% of the variance. Both mothers and fathers exert notable influences, exceeding those suggested in previous studies. Moreover, positive gene-environment correlations between parents and offspring show that the intrafamilial environment and childrens genetic predisposition are dependent and mutually reinforcing.

genetics↗

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↗

bioRxiv2023

Genetic and brain similarity independently predict childhood anthropometrics and socioeconomic markers

Linking the developing brain with individual differences in clinical and demographic traits is challenging due to the substantial interindividual heterogeneity of brain anatomy and organization. Here we employ a novel approach that parses individual differences in both cortical thickness and common genetic variants, and assess their effects on a wide set of childhood traits. The approach uses a linear mixed model framework to obtain the unique effects of each type of similarity, as well as their covariance, with the assumption that similarity in cortical thickness may in part be driven by similarity in genetic variants. We employ this approach in a sample of 7760 unrelated children in the ABCD cohort baseline sample (mean age 9.9, 46.8% female). In general, significant associations between cortical thickness similarity and traits were limited to anthropometrics such as height (r2 = 0.11, SE = 0.01), weight (r2 = 0.12, SE = 0.01), and birth weight (r2 = 0.19, SE = 0.01), as well as markers of socioeconomic status such as local area deprivation (r2 = 0.06, SE = 0.01). Analyses of the contribution from common genetic variants to traits revealed contributions across included outcomes, albeit somewhat lower than previous reports, possibly due to the young age of the sample. No significant covariance of the effects of genetic and cortical thickness similarity was found. The present findings highlight the connection between anthropometrics as well as socioeconomic factors and the developing brain, which appear to be independent from individual differences in common genetic variants in this population-based sample. The approach provides a promising framework for analyses of neuroimaging genetics cohorts, which can be further expanded by including imaging derived phenotypes beyond cortical thickness.

neuroscience↗

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↗

bioRxiv2020

Disentangling principled and opportunistic motives for reacting to injustice: A genetically-informed exploration of justice sensitivity

Moral judgments may be driven by both principled and opportunistic motivations. Being morally principled is to consistently adhere to a single set of rules about morality and justice. Opportunistic morality rather involves selectively enforcing rules when they are beneficial to ones interests. These two kinds of motivations sometimes pull in the same direction, other times not. Prior studies on moral motivations have mostly focused on principled morality. Opportunistic morality, along with its phenotypic and genetic correlates, remains largely unexamined. Here, utilizing a sample from the Norwegian Twin Registry, consisting of 312 monozygotic-and 298 dizygotic twin pairs (N = 1220), we measure peoples propensity to react to injustice as victims, observers, beneficiaries, and perpetrators of injustice, using the Justice Sensitivity scale. Our genetically informative sample allows a biometric modeling approach that provides increased stringency in inferring latent psychological traits. We find evidence for two substantially heritable traits explaining correlations between Justice Sensitivity facets, which we interpret as a principled justice sensitivity (h2 = .45) leading to increased sensitivity to injustices of all categories, and an opportunistic justice sensitivity (h2 = .69) associated with increased victim sensitivity and a decreased propensity to feel guilt from being a perpetrator. These heritable justice traits share a genetic substrate with broad strategies for cooperation (as measured by altruism and trust) and for selectively benefitting oneself over the adaptive interests of others (as measured by social dominance orientation and support for monopolizing territory and resources), and differ genetically and phenotypically from Big Five personality traits.

genetics↗

bioRxiv2020

Direct and indirect effects of maternal, paternal, and offspring genotypes: Trio-GCTA

Indirect genetic effects from relatives may result in misleading quantifications of heritability, but can also be of interest in their own right. In this paper we propose Trio-GCTA, a model for separating direct and indirect genetic effects when genome-wide single nucleotide polymorphism data have been collected from parent-offspring trios. The model is applicable to phenotypes obtained from any of the family members. We discuss appropriate parameter interpretations and apply the method to four exemplar phenotypes; offspring birth weight, offspring temperament, maternal relationship satisfaction, and paternal body-mass index, using real data from the Norwegian Mother, Father and Child Cohort Study (MoBa).

genetics↗