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

Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study DOI Creative Commons
Leonard Frach, Wikus Barkhuizen, Andrea G. Allegrini

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(4), P. 951 - 961

Published: Jan. 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.

Language: Английский

Citations

7
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
The genetics of specific cognitive abilities DOI Creative Commons
Francesca Procopio, Quan Zhou,

Ziye Wang

et al.

Intelligence, Journal Year: 2022, Volume and Issue: 95, P. 101689 - 101689

Published: Sept. 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

Language: Английский

Citations

27
Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study DOI Creative Commons
Laurence J Howe, Humaira Rasheed, Paul Remy Jones

et al.

International Journal of Epidemiology, Journal Year: 2023, Volume and Issue: 52(5), P. 1579 - 1591

Published: June 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.

Language: Английский

Citations

16
Evaluating indirect genetic effects of siblings using singletons DOI Creative Commons
Laurence J Howe, David M. Evans, Gibran Hemani

et al.

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(7), P. e1010247 - e1010247

Published: July 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.

Language: Английский

Citations

21
Annual Research Review: Towards a deeper understanding of nature and nurture: combining family‐based quasi‐experimental methods with genomic data DOI Creative Commons
Tom A. McAdams, Rosa Cheesman, Yasmin I. Ahmadzadeh

et al.

Journal of Child Psychology and Psychiatry, Journal Year: 2022, Volume and Issue: 64(4), P. 693 - 707

Published: Nov. 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.

Language: Английский

Citations

20
Evaluating the causal relationship between educational attainment and mental health DOI Creative Commons
Perline Demange, Dorret I. Boomsma, Elsje van Bergen

et al.

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

Published: Jan. 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.

Language: Английский

Citations

12
The importance of family-based sampling for biobanks DOI
Neil M Davies, Gibran Hemani, Jenae M. Neiderhiser

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8035), P. 795 - 803

Published: Oct. 23, 2024

Language: Английский

Citations

4
Does test preparation mediate the effect of parents' level of educational attainment on medical school admission test performance? DOI Creative Commons
Markus Sommer,

Martin Arendasy,

Joachim Fritz Punter

et al.

Intelligence, Journal Year: 2025, Volume and Issue: 108, P. 101893 - 101893

Published: Jan. 1, 2025

Language: Английский

Citations

0
Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design DOI Creative Commons
Xiaoyi Li, Zechen Zhou, Yujia Ma

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 120 - 120

Published: Jan. 7, 2025

Background/Objectives: Genes and environments were transmitted across generations. Parents' genetics influence the of their offspring; these two modes inheritance can produce a genetic nurture effect, also known as indirect effects. Such effects may partly account for estimated variance in T2D. However, well-established specific risk factors about effect T2D are not fully understood. This study aimed to investigate on type 2 diabetes reveal potential underlying mechanism using publicly available data. Methods: Whole-genome genotyping data 881 offspring and/or parents collected. We assessed SNP-level, gene-based, pathway-based associations different types Results: Rs3805116 (β: 0.54, p = 4.39 × 10-8) was significant paternal MRPS33 (p 1.58 10-6), PIH1D2 6.76 10-7), SD1HD 2.67 10-6) revealed significantly positive Five ontologies identified enrichment both direct effects, including flavonoid metabolic process antigen processing presentation via MHC class Ib pathway. Two pathways only enriched transforming growth factor beta Tissue diabetes-associated genes performed gene expression from Human Protein Atlas database. observed gallbladder, smooth muscle, adrenal gland tissues. Conclusions: MRPS33, PIH1D2, associated with increased through environment influenced by genotype, suggesting novel perspective contributions predisposition.

Language: Английский

Citations

0