The genetics of low and high birthweight and their relationship with cardiometabolic disease DOI Creative Commons
Gunn-Helen Moen, Liang‐Dar Hwang, Caroline Brito Nunes

et al.

Diabetologia, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Aims/hypothesis Low birthweight infants are at increased risk not only of mortality, but also type 2 diabetes mellitus and CVD in later life. At the opposite end spectrum, high have birth complications, such as shoulder dystocia, neonatal hypoglycaemia obesity, similarly CVD. However, previous genome-wide association studies (GWAS) UK Biobank primarily focused on individuals within ‘normal’ range excluded with low (<2.5 kg or >4.5 kg). The aim this study was to investigate genetic variation associated tail ends distribution, to: (1) see whether factors operating these regions were different from those that explained normal range; (2) explore correlation between extremes cardiometabolic disease; (3) analysing full distribution values, including extremes, improved ability detect genuine loci GWAS. Methods We performed case–control GWAS analysis kg) (>4.5 using REGENIE software ( N =20,947; =12,715; controls =207,506) conducted three continuous birthweight, one birthweights, involving a truncated birthweights 2.5 4.5 third winsorised values <2.5 kg. Additionally, we bivariate linkage disequilibrium (LD) score regression estimate low/normal/high traits. Results Bivariate LD analyses suggested had mostly similar aetiology (genetic coefficient [ r G ]=0.91, 95% CI 0.83, 0.99), whereas there more evidence for separate set genes underlying =−0.74, 0.66, 0.82). significantly positively genetically correlated most traits diseases examined, adiposity anthropometric-related winsorisation strategy best terms locus detection, number independent significant associations p <5×10 −8 ) increasing 120 variants 94 270 178 loci, 27 25 been identified This included novel low-frequency missense variant ABCC8 gene, gene known be involved congenital hyperinsulinism, MODY, estimated responsible 170 g increase amongst carriers. Conclusions/interpretation Our results underscore importance genesis phenotypic diseases. Graphical

Language: Английский

Interpreting population- and family-based genome-wide association studies in the presence of confounding DOI Creative Commons
Carl Veller, Graham Coop

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(4), P. e3002511 - e3002511

Published: April 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

Language: Английский

Citations

31
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
Gene–environment interactions in human health DOI

Esther Herrera-Luis,

Kelly S. Benke, Heather E. Volk

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: 25(11), P. 768 - 784

Published: May 28, 2024

Language: Английский

Citations

19
Robust genetic nurture effects on education: A systematic review and meta-analysis based on 38,654 families across 8 cohorts DOI
Biyao Wang, Jessie R. Baldwin, Tabea Schoeler

et al.

The American Journal of Human Genetics, Journal Year: 2021, Volume and Issue: 108(9), P. 1780 - 1791

Published: Aug. 19, 2021

Language: Английский

Citations

84
Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores DOI Creative Commons
Perline Demange, Jouke‐Jan Hottenga, Abdel Abdellaoui

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 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.

Language: Английский

Citations

64
Genetic similarity between relatives provides evidence on the presence and history of assortative mating DOI Creative Commons
Hans Fredrik Sunde, Nikolai Haahjem Eftedal, Rosa Cheesman

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 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.

Language: Английский

Citations

13
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
Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study DOI Creative Commons
Jean‐Baptiste Pingault, Wikus Barkhuizen, Biyao Wang

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(4), P. 1731 - 1738

Published: Nov. 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.

Language: Английский

Citations

37
Interpreting population and family-based genome-wide association studies in the presence of confounding DOI Creative Commons
Carl Veller, Graham Coop

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

Published: Feb. 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.

Language: Английский

Citations

20
Why we need families in genomic research on developmental psychopathology DOI
Rosa Cheesman, Ziada Ayorech, Espen Moen Eilertsen

et al.

JCPP Advances, Journal Year: 2023, Volume and Issue: 3(1)

Published: Jan. 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.

Language: Английский

Citations

19