Interpreting population- and family-based genome-wide association studies in the presence of confounding

PLoS Biology, Год журнала: 2024, Номер 22(4), С. e3002511 - e3002511

Опубликована: Апрель 11, 2024

A central aim of genome-wide association studies (GWASs) is to estimate direct genetic effects: the causal effects on an individual’s phenotype alleles that they carry. However, estimates can be subject and environmental confounding also absorb “indirect” relatives’ genotypes. Recently, important development in controlling for these confounds has been use within-family GWASs, which, because randomness mendelian segregation within pedigrees, are often interpreted as producing unbiased effects. Here, we present a general theoretical analysis influence standard population-based GWASs. We show that, contrary common interpretation, family-based biased by confounding. In humans, such biases will small per-locus, but compounded when effect-size used polygenic scores (PGSs). illustrate population- using models assortative mating, population stratification, stabilizing selection GWAS traits. further how indirect effects, based comparisons parentally transmitted untransmitted alleles, suffer substantial conclude while have placed estimation more rigorous footing, carry subtle issues interpretation arise from

Язык: Английский

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More than nature and nurture, indirect genetic effects on children’s academic achievement are consequences of dynastic social processes

Nature Human Behaviour, Год журнала: 2024, Номер 8(4), С. 771 - 778

Опубликована: Янв. 15, 2024

Язык: Английский

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Gene–environment interactions in human health

Nature Reviews Genetics, Год журнала: 2024, Номер 25(11), С. 768 - 784

Опубликована: Май 28, 2024

Язык: Английский

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Robust genetic nurture effects on education: A systematic review and meta-analysis based on 38,654 families across 8 cohorts

The American Journal of Human Genetics, Год журнала: 2021, Номер 108(9), С. 1780 - 1791

Опубликована: Авг. 19, 2021

Язык: Английский

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Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 23, 2022

Understanding how parents' cognitive and non-cognitive skills influence offspring education is essential for educational, family economic policy. We use genetics (GWAS-by-subtraction) to assess a latent, broad dimension. To index parental effects controlling genetic transmission, we estimate indirect of polygenic scores on childhood adulthood educational outcomes, using siblings (N = 47,459), adoptees 6407), parent-offspring trios 2534) in three UK Dutch cohorts. find that affect through their environment: average across cohorts designs, explain 36-40% population score associations. However, are lower achievement the cohort, adoption design. identify potential causes higher sibling- trio-based estimates: prenatal effects, stratification, assortative mating. Our phenotype-agnostic, genetically sensitive approach has established overall environmental skills, facilitating future mechanistic work.

Язык: Английский

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

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 26, 2024

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

Язык: Английский

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Examining the role of common variants in rare neurodevelopmental conditions

Nature, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

Abstract Although rare neurodevelopmental conditions have a large Mendelian component 1 , common genetic variants also contribute to risk 2,3 . However, little is known about how this polygenic distributed among patients with these and their parents nor its interplay variants. It unclear whether background affects directly through alleles transmitted from children, or indirect effects mediated the family environment 4 play role. Here we addressed questions using data 11,573 conditions, 9,128 of 26,869 controls. Common explained around 10% variance in risk. Patients monogenic diagnosis had significantly less than those without, supporting liability threshold model 5 A score for showed only direct effect. By contrast, scores educational attainment cognitive performance no effect, but non-transmitted were correlated child’s risk, potentially due and/or parental assortment traits Indeed, as expected under assortment, show that variant predisposition These findings indicate future studies should investigate possible role nature on consider contribution simultaneously when studying cognition-related phenotypes.

Язык: Английский

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Multi-source physical information driven deep learning in intelligent education: Unleashing the potential of deep neural networks in complex educational evaluation

AIP Advances, Год журнала: 2025, Номер 15(2)

Опубликована: Фев. 1, 2025

With the urgent global demand for sustainable development, intelligent education driven by multi-source physical information has attracted widespread attention as an innovative educational model. However, in context of dual carbon, achieving and efficient development faces many difficulties, one important challenges is how to effectively evaluate students. The application deep neural networks evaluation direction digitization. Currently, there need conduct research on value empowering with networks. We first studied principles characteristics network technology evaluation; second, three major advantages were pointed out: objectivity evaluating diversified data, accuracy perception information, mining data finally, key faced clarified from perspectives environment, theoretical knowledge, interpretability. This provides new ideas methods lays foundation breaking through traditional era carbon development.

Язык: Английский

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Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study

Molecular Psychiatry, Год журнала: 2022, Номер 28(4), С. 1731 - 1738

Опубликована: Ноя. 16, 2022

Abstract Identifying mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) traits can inform interventions and provide insights into role parents in shaping their children’s outcomes. We investigated whether genetic nurture (environmentally mediated effects) underlie associations between polygenic scores indexing parental protective factors offspring’s ADHD traits. This birth cohort study included 19,506 genotyped mother-father-offspring trios from Norwegian Mother, Father Child Cohort Study. Polygenic were calculated previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment, cognitive performance. Mothers reported on 8-year-old ( n = 9,454 children) using Parent/Teacher Rating Scale Disruptive Behaviour Disorders. found that maternal paternal child decreased significantly when adjusting score p Δβ 9.95 × 10 −17 1.48 −14 estimates), suggesting risk. Similar patterns observed smoking, cognition. The neuroticism remained ratings even after score, indicating nurture. There was no robust evidence other factors. Our findings indicate is largely explained by variants to offspring rather than Observational childhood outcomes should not be interpreted as predominantly environmentally effects.

Язык: Английский

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Interpreting population and family-based genome-wide association studies in the presence of confounding

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

Опубликована: Фев. 27, 2023

Abstract A central aim of genome-wide association studies (GWASs) is to estimate direct genetic effects: the causal effects on an individual’s phenotype alleles that they carry. However, estimates can be subject and environmental confounding, also absorb ‘indirect’ relatives’ genotypes. Recently, important development in controlling for these confounds has been use within-family GWASs, which, because randomness Mendelian segregation within pedigrees, are often interpreted as producing unbiased effects. Here, we present a general theoretical analysis influence confounding standard population-based GWASs. We show that, contrary common interpretation, family-based biased by confounding. In humans, such biases will small per-locus, but compounded when effect size used polygenic scores. illustrate population- using models assortative mating, population stratification, stabilizing selection GWAS traits. further how indirect effects, based comparisons parentally transmitted untransmitted alleles, suffer substantial addition known arise GWASs interactions between family members ignored, from gene-by-environment (G×E) parental genotypes not distributed identically across interacting backgrounds. conclude while have placed estimation more rigorous footing, carry subtle issues interpretation interactions.

Язык: Английский

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