Why we need families in genomic research on developmental psychopathology

JCPP Advances, Год журнала: 2023, Номер 3(1)

Опубликована: Янв. 27, 2023

Fundamental questions about the roles of genes, environments, and their interplay in developmental psychopathology have traditionally been domain twin family studies. More recently, rapidly growing availability large genomic datasets, composed unrelated individuals, has generated novel insights. However, there are major stumbling blocks. Only a small fraction total genetic influence on childhood estimated from data is captured with measured DNA. Moreover, identified using DNA often confounded indirect effects relatives, population stratification assortative mating.

Язык: Английский

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Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study

Molecular Psychiatry, Год журнала: 2024, Номер 29(4), С. 951 - 961

Опубликована: Янв. 16, 2024

The aetiology of conduct problems involves a combination genetic and environmental factors, many which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important disentangle what extent links between heritable behaviour due transmission risk or indirect influences via the environment (i.e., nurture). We used 31,290 genotyped mother-father-child trios from Norwegian Mother, Father Child Cohort Study (MoBa), testing nurture effects on using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related other factors. Maternal self-reports at ages 8 14 years were available for up 15,477 children. found significant 12 out PGS age (strongest association: smoking, β = 0.07, 95% confidence interval [0.05, 0.08]) 4 externalising problems, 0.08, 0.11]). Conversely, we did not find our selection PGS. Our findings provide evidence association child problems. results may also indicate that traits indexed by limited aetiological importance problems-though small magnitude captured included remain possibility.

Язык: Английский

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The genetics of specific cognitive abilities

Intelligence, Год журнала: 2022, Номер 95, С. 101689 - 101689

Опубликована: Сен. 22, 2022

Most research on individual differences in performance tests of cognitive ability focuses general (g), the highest level three-level Cattell-Horn-Carroll (CHC) hierarchical model intelligence. About 50% variance g is due to inherited DNA (heritability) which increases across development. Much less known about genetics middle CHC model, includes 16 broad factors such as fluid reasoning, processing speed, and quantitative knowledge. We provide a meta-analytic review 747,567 monozygotic-dizygotic twin comparisons from 77 publications for these middle-level factors, we refer specific abilities (SCA), even though are not independent g. Twin were available 11 domains. The average heritability all SCA 56%, similar that However, there substantial differential do show developmental increase seen also investigated (SCA.g). A surprising finding SCA.g remain substantially heritable (53% average), 25% covaries with has been removed. Our highlights need more especially SCA.g. Despite limitations research, our frames expectations genomic will use polygenic scores predict Genome-wide association studies needed create can profiles disabilities

Язык: Английский

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Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study

International Journal of Epidemiology, Год журнала: 2023, Номер 52(5), С. 1579 - 1591

Опубликована: Июнь 9, 2023

Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these may been susceptible to bias stratification, assortative mating and indirect genetic due unadjusted parental genotypes. MR association derived within-sibship models (within-sibship can avoid potential biases because differences between siblings are random segregation at meiosis.

Язык: Английский

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Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 6, 2024

Abstract Although rare neurodevelopmental conditions have a large Mendelian component, common genetic variants also contribute to risk. However, little is known about how this polygenic risk distributed among patients with these and their parents, its interplay variants, whether parents’ background contributes children’s beyond the direct effect of transmitted child (i.e. via indirect effects potentially mediated through prenatal environment or ‘genetic nurture’). Here, we addressed questions using data from 11,573 conditions, 9,128 parents 26,869 controls. Common explained ∼10% variance in overall Patients monogenic diagnosis had significantly less than those without, supporting liability threshold model, while both genetically undiagnosed diagnosed affected more In trio-based score for but not non-transmitted parental alleles were associated risk, indicating effect. contrast, observed no scores educational attainment cognitive performance, saw significant correlation between child’s due and/or assortment traits. Indeed, as expected under assortment, show that variant predisposition correlated component Our findings thus suggest future studies should investigate possible role nature on consider contribution simultaneously when studying cognition-related phenotypes.

Язык: Английский

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Evaluating indirect genetic effects of siblings using singletons

PLoS Genetics, Год журнала: 2022, Номер 18(7), С. e1010247 - e1010247

Опубликована: Июль 7, 2022

Estimating effects of parental and sibling genotypes (indirect genetic effects) can provide insight into how the family environment influences phenotypic variation. There is growing molecular evidence for phenotypes on their offspring (e.g. educational attainment), but extent to which siblings affect each other currently unclear. Here we used data from samples unrelated individuals, without (singletons) with biological full-siblings (non-singletons), investigate estimate effects. Indirect increase (or decrease) covariance between variation a phenotype. It follows that differences in association estimates singletons non-singletons could indicate indirect if there no heterogeneity sources non-singletons. We UK Biobank polygenic score (PGS) associations height, BMI attainment self-reported (N = 50,143) 328,549). The PGS was 12% larger (95% C.I. 3%, 21%) non-singleton sample than singleton sample, height were consistent. Birth order suggested difference driven by individuals older rather firstborns. relationship number non-linear; 24% smaller 6 or more compared rest 11%, 38%). 1 SD corresponds 0.025 year index individual's years schooling 0.013, 0.036). Our results suggest may influence younger siblings, adding partially reflect social germline relatives.

Язык: Английский

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Annual Research Review: Towards a deeper understanding of nature and nurture: combining family‐based quasi‐experimental methods with genomic data

Journal of Child Psychology and Psychiatry, Год журнала: 2022, Номер 64(4), С. 693 - 707

Опубликована: Ноя. 15, 2022

Distinguishing between the effects of nature and nurture constitutes a major research goal for those interested in understanding human development. It is known, example, that many parent traits predict mental health outcomes children, but causal processes underlying such associations are often unclear. Family‐based quasi‐experimental designs as sibling comparison, adoption extended family studies have been used decades to distinguish genetic transmission risk from environmental members potentially on one another. Recently, these combined with genomic data, this combination fuelling range exciting methodological advances. In review we explore advances – highlighting ways which they applied date considering what likely teach us coming years about aetiology intergenerational psychopathology.

Язык: Английский

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Evaluating the causal relationship between educational attainment and mental health

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 26, 2023

We investigate the causal relationship between educational attainment (EA) and mental health using two research designs. First, we compare EA 18 psychiatric diagnoses within sibship in Dutch national registry data (N=1.7 million), thereby controlling for unmeasured familial factors. Second, apply two-sample Mendelian Randomization, which uses genetic variants related to or diagnosis as instrumental variables, test whether there is a relation either direction. Our results suggest that lower levels of causally increase risk MDD, ADHD, alcohol dependence, GAD PTSD diagnoses. also find evidence effect ADHD on EA. For schizophrenia, anorexia nervosa, OCD, bipolar disorder, were inconsistent across different approaches, highlighting importance multiple designs understand complex relationships such health.

Язык: Английский

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The importance of family-based sampling for biobanks

Nature, Год журнала: 2024, Номер 634(8035), С. 795 - 803

Опубликована: Окт. 23, 2024

Язык: Английский

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Educational attainment and psychiatric diagnoses: a national registry data and two-sample Mendelian randomization study

Nature Mental Health, Год журнала: 2024, Номер 2(6), С. 668 - 679

Опубликована: Май 2, 2024

Язык: Английский

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