Mendelian Randomization: Concepts and Scope

Cold Spring Harbor Perspectives in Medicine, Год журнала: 2021, Номер 12(1), С. a040501 - a040501

Опубликована: Авг. 23, 2021

Mendelian randomization (MR) is a method of studying the causal effects modifiable exposures (i.e., potential risk factors) on health, social, and economic outcomes using genetic variants associated with specific interest. MR provides more robust understanding influence these because germline are randomly inherited from parents to offspring and, as result, should not be related confounding factors that exposure-outcome associations. The variant can therefore used tool link proposed factor outcome, estimate this effect less bias than conventional epidemiological approaches. We describe scope MR, highlighting range applications being made possible data sets resources become larger freely available. outline approach in detail, covering concepts, assumptions, estimation methods. cover some common misconceptions, provide strategies for overcoming violation discuss future prospects extending clinical applicability, methodological innovations, robustness, generalizability findings.

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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The impact of digital media on children’s intelligence while controlling for genetic differences in cognition and socioeconomic background

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Май 11, 2022

Abstract Digital media defines modern childhood, but its cognitive effects are unclear and hotly debated. We believe that studies with genetic data could clarify causal claims correct for the typically unaccounted role of predispositions. Here, we estimated impact different types screen time (watching, socializing, or gaming) on children’s intelligence while controlling confounding differences in cognition socioeconomic status. analyzed 9855 children from USA who were part ABCD dataset measures at baseline (ages 9–10) after two years. At baseline, watching (r = − 0.12) socializing 0.10) negatively correlated intelligence, gaming did not correlate. After years, positively impacted (standardized β + 0.17), had no effect. This is consistent benefits documented experimental video gaming. Unexpectedly, videos also benefited 0.12), contrary to prior research effect TV. Although, a posthoc analysis, this was significant if parental education (instead SES) controlled for. Broadly, our results line malleability abilities environmental factors, such as training Flynn

Язык: Английский

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Research Review: How to interpret associations between polygenic scores, environmental risks, and phenotypes

Journal of Child Psychology and Psychiatry, Год журнала: 2022, Номер 63(10), С. 1125 - 1139

Опубликована: Март 28, 2022

Background Genetic influences are ubiquitous as virtually all phenotypes and most exposures typically classified environmental have been found to be heritable. A polygenic score summarises the associations between millions of genetic variants an outcome in a single value for each individual. Ever lowering costs enabled genotyping many samples relevant child psychology psychiatry research, including cohort studies, leading proliferation studies. It is tempting assume that detected scores those studies only reflect effects. However, such can pathways (e.g. via mediation) biases. Methods Here, we provide comprehensive overview reasons why scores, exposures, exist. We include formal representations common analyses using structural equation modelling. derive biases, illustrative empirical examples and, when possible, mention steps taken alleviate Results Structural models derivations show complexities arising from jointly modelling with phenotypes. Counter‐intuitive that: (a) may exist even absence direct effects; (b) evocative/active gene–environment correlations; (c) adjusting exposure‐outcome association increase rather than decrease bias. Conclusions Strikingly, may, some cases, lead more bias not them. Appropriately conducting interpreting thus requires researchers beyond versed both epidemiological methods or build on interdisciplinary collaborations.

Язык: Английский

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Maximizing the value of twin studies in health and behaviour

Nature Human Behaviour, Год журнала: 2023, Номер 7(6), С. 849 - 860

Опубликована: Май 15, 2023

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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Exome sequencing identifies genes for socioeconomic status in 350,770 individuals

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(2)

Опубликована: Янв. 7, 2025

Socioeconomic status (SES) is a critical factor in determining health outcomes and influenced by genetic environmental factors. However, our understanding of the structure SES remains incomplete. Here, we conducted large-scale exome study markers (household income, occupational status, educational attainment, social deprivation) 350,770 individuals. For rare coding variants, identified 56 significant associations gene-based collapsing tests, unveiling 7 additional SES-associated genes ( NRN1 , CCDC36 RHOB EP400 NCAM1, TPTEP2-CSNK1E LINC02881 ). Exome-wide single common variant analysis revealed nine lead single-nucleotide polymorphisms (SNPs) associated with household income 34 SNPs EduYears, replicating previous GWAS findings. The gene–environment correlations had substantial impact on SES, as indicated significantly increased P values several after controlling for geographic regions. Furthermore, observed pleiotropic effects factors wide range outcomes, such cognitive function, psychosocial diabetes. This highlights contribution variants to their phenotypes.

Язык: Английский

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Genetic sensitivity analysis: Adjusting for genetic confounding in epidemiological associations

PLoS Genetics, Год журнала: 2021, Номер 17(6), С. e1009590 - e1009590

Опубликована: Июнь 11, 2021

Associations between exposures and outcomes reported in epidemiological studies are typically unadjusted for genetic confounding. We propose a two-stage approach estimating the degree to which such observed associations can be explained by First, we assess attenuation of exposure effects regressions controlling increasingly powerful polygenic scores. Second, use structural equation models estimate confounding using heritability estimates derived from both SNP-based twin-based studies. examine maternal education three developmental – child educational achievement, Body Mass Index, Attention Deficit Hyperactivity Disorder. Polygenic scores explain 14.3% 23.0% original associations, while analyses under SNP- scenarios indicate that could almost entirely Thus, caution is needed when interpreting non-genetically informed epidemiology Our approach, akin genetically sensitivity analysis applied widely.

Язык: Английский

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Social and genetic associations with educational performance in a Scandinavian welfare state

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(25)

Опубликована: Июнь 16, 2022

Recent research has suggested that across Western developed societies, the influence of genetics on educational outcomes is relatively constant. However, degree to which family environment matters varies, such countries with high levels intergenerational mobility have weaker associations background. Research in this vein relied twin-based estimates, involve variance decomposition, so direct assessment association genes and environments not possible. In present study, we approach question by directly measuring impact child genotype, parental genetic nurture, realized education achievement primary secondary school. We deploy data from a social democratic context (Norway) contrast our findings those derived more liberal welfare state contexts. Results point only confounding relationship between parent status offspring small degree. Genetic nurture are similar other societies. find no, or very small, gene–environment interactions parent–child genotype respect test scores. sum, Scandinavian context, both environmental magnitude as societies less-robust efforts mitigate

Язык: Английский

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Cross-National and Cross-Generational Evidence That Educational Attainment May Slow the Pace of Aging in European-Descent Individuals

The Journals of Gerontology Series B, Год журнала: 2023, Номер 78(8), С. 1375 - 1385

Опубликована: Апрель 14, 2023

Individuals with more education are at lower risk of developing multiple, different age-related diseases than their less-educated peers. A reason for this might be that individuals age slower. There 2 complications in testing hypothesis. First, there exists no definitive measure biological aging. Second, shared genetic factors contribute toward both educational attainment and the development diseases. Here, we tested whether protective effect was associated pace aging after accounting factors.

Язык: Английский

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