Intergenerational transmission of polygenic predisposition for neuropsychiatric traits on emotional and behavioural difficulties in childhood DOI Open Access
Andrea G. Allegrini, Laurie J. Hannigan, Leonard Frach

et al.

Published: Nov. 21, 2023

Childhood emotional and behavioural difficulties frequently co-occur often precede diagnosed neuropsychiatric conditions. Delineating shared specific risk factors for early in life is therefore essential prevention strategies. Here, we focus on how a set of key parental shape their offspring’s symptoms. Leveraging data from 14,959 genotyped family trios the Norwegian Mother, Father Child Cohort Study (MoBa), model symptom level into general domains. We then investigate direct (genetically transmitted) indirect (environmentally mediated) contributions polygenic related traits to observe evidence consistent with an environmental route symptomatology beyond genetic transmission, while also demonstrating domain-specific contributions. Our findings pave way better identification pathways that can be targeted preventive interventions aiming interrupt intergenerational cycle transmission.

Language: Английский

More than nature and nurture, indirect genetic effects on children’s academic achievement are consequences of dynastic social processes DOI
Michel G. Nivard, Daniel W. Belsky, K. Paige Harden

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(4), P. 771 - 778

Published: Jan. 15, 2024

Language: Английский

Citations

27
Examining the role of common variants in rare neurodevelopmental conditions DOI Creative Commons
Qin Qin Huang, Emilie M. Wigdor, Daniel Malawsky

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Citations

10
A Litmus Test for Confounding in Polygenic Scores DOI Creative Commons
Samuel Pattillo Smith, Olivia S. Smith, Hakhamanesh Mostafavi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Abstract Polygenic scores (PGSs) are being rapidly adopted for trait prediction in the clinic and beyond. PGSs often thought of as capturing direct genetic effect one’s genotype on their phenotype. However, because constructed from population-level associations, they influenced by factors other than effects, including stratification, assortative mating, dynastic effects (“SAD effects”). Our interpretation application may hinge relative impact SAD since be environmentally or culturally mediated. We developed a method that estimates proportion variance PGS (in given sample) is driven covariance. leverage comparison interest based standard GWAS with sibling GWAS—which largely immune to effects—to quantify contribution each type interest. method, Partitioning Genetic Scores Using Siblings (PGSUS, pron. “Pegasus”), breaks down components further axes ancestry, allowing nuanced effects. In particular, PGSUS can detect stratification along major ancestry well “isotropic” respect ancestry. Applying PGSUS, we found evidence using large meta-analyses height educational attainment range UK Biobank. some instances, appears stratified axis one sample but not another (for example, comparisons samples different countries, ancient DNA vs. contemporary samples). Finally, show approaches adjustment population structure GWASs have distinct advantages mitigation ancestry-axis-specific isotropic PGS. study illustrates how family-based designs combined population-based guide genomic predictors.

Language: Английский

Citations

1
Dissecting the contribution of common variants to risk of rare neurodevelopmental conditions DOI Creative Commons
Qin Qin Huang, Emilie M. Wigdor,

Patrick Campbell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

6
Social-Science Genomics: Progress, Challenges, and Future Directions DOI Open Access
Daniel J. Benjamin, David Cesarini, Patrick Turley

et al.

Published: May 1, 2024

Rapid progress has been made in identifying links between human genetic variation and social behavioral phenotypes.Applications mainstream economics are beginning to emerge.This review aims provide the background needed bring interested economist frontier of social-science genomics.Our is structured around a theoretical framework that nests many key methods, concepts tools found literature.We clarify assumptions appropriate interpretations.After reviewing several significant applications, we conclude by outlining future advances genetics will expand scope potential discuss ethical communication challenges arise this area research.

Language: Английский

Citations

6
Intergenerational transmission of polygenic predisposition for neuropsychiatric traits on emotional and behavioural difficulties in childhood DOI Creative Commons
Andrea G. Allegrini, Laurie J. Hannigan, Leonard Frach

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 18, 2025

Abstract Childhood emotional and behavioural difficulties tend to co-occur often precede diagnosed neuropsychiatric conditions. Identifying shared specific risk factors for early-life mental health is therefore essential prevention strategies. Here, we examine how parental shape their offspring’s symptoms (e.g. feelings of anxiety, restlessness) using data from 14,959 genotyped family trios the Norwegian Mother, Father Child Cohort Study (MoBa). We model maternal reports symptoms, organizing them into general domains. then investigate direct (genetically transmitted) indirect (environmentally mediated) contributions polygenic neuropsychiatric-related traits whether these are across symptoms. observe evidence consistent with an environmental route symptomatology beyond genetic transmission, while also demonstrating domain-specific contributions. These findings improve our understanding early pathways that can be targeted in preventive interventions aiming interrupt intergenerational cycle transmission.

Language: Английский

Citations

0
Socio-economic status is a social construct with heritable components and genetic consequences DOI
Abdel Abdellaoui, Hilary C. Martin, Martin Kolk

et al.

Nature Human Behaviour, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Language: Английский

Citations

0
Social Background Effects on Educational Outcomes—New Insights from Modern Genetic Science DOI Creative Commons
Tina Baier, Torkild Hovde Lyngstad

KZfSS Kölner Zeitschrift für Soziologie und Sozialpsychologie, Journal Year: 2024, Volume and Issue: 76(3), P. 525 - 545

Published: Sept. 1, 2024

Language: Английский

Citations

1
Confounding Fuels Misinterpretation in Human Genetics DOI Creative Commons
John W. Benning, Jedidiah Carlson, Olivia S. Smith

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 3, 2023

The scientific literature has seen a resurgence of interest in genetic influences on human behavior and socioeconomic outcomes. Such studies face the central difficulty distinguishing possible causal influences, particular non-genetic ones. When confounding between is not rigorously addressed, it invites over- misinterpretation data. We illustrate breadth this problem through discussion reanalysis two examples. Clark (2023) suggested that patterns similarity social status relatives indicate largely determined by one's DNA. show paper's conclusions are based conflation transmission, such as wealth, within families. Song & Zhang (2024) posited variants underlying bisexual maintained population because they also affect risk-taking behavior, thereby conferring an evolutionary fitness advantage increased sexual promiscuity. In case, too, we explanations cannot be distinguished, but only one chosen presented conclusion. discuss how issues apply more broadly to claim establish underpinnings societal

Language: Английский

Citations

3
Assessing the impact of 20th century internal migrations on the genetic structure of Estonia DOI Creative Commons
Ivan A. Kuznetsov, Mait Metspalu, Uku Vainik

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 29, 2023

Abstract Spatial genetic structure observed in many human populations is large part attributed to past demographic events and isolation by distance. However, how intensifying migration affects this remains understudied. Here we harness a sample of more than 180 thousand individuals explore the correlates consequences contemporary migrations Estonia. While show that smoothens genome-wide structure, it intensifies inter-regional differences polygenic scores (PGS) for certain traits, derived both from population as well within-sibship studies. The strongest effect educational attainment which consistent with previous observations UK suggests be general pattern. We those regional PGS terms driving forces behind them temporal perspective, suggest urbanisation major driver pattern Estonia at least first half 20th century.

Language: Английский

Citations

3