Biology subjects

Bann, D.

Publications and source records attributed to Bann, D..

6 recordsLinked to original sources

bioRxiv2025

An Updated Polygenic Index Repository: Expanded Phenotypes, New Cohorts, and Improved Causal Inference

Polygenic indexes (PGIs) -- DNA-based predictors of individual phenotypes -- have become essential tools across biomedical and social sciences. We introduce Version 2 of the Polygenic Index Repository, which expands phenotype coverage from 47 to 61, increases the number of participating datasets from 11 to 20, and adopts a more consistent and improved methodology for PGI construction. For 16 phenotypes, we leverage summary statistics from an updated GWAS meta-analysis with greater statistical power compared to the original release, thereby improving the PGIs predictive power. To improve power for family-based analyses, we provide imputed parental PGIs in all datasets with first-degree relatives and offer a framework for interpreting results from analyses that control for parental PGIs. We illustrate the utility of parental PGIs using two applications: (1) comparing PGI associations with and without parental PGI controls for all phenotypes in two Repository datasets with family data, and (2) for BMI and diastolic blood pressure, exploring the contribution of causal versus non-causal components of PGI associations to the imperfect portability of PGIs across subgroups within a genetic ancestry. Collectively, the updates enhance predictive performance, broaden the Repositorys scope, and introduce novel resources that reduce confounding bias and improve interpretability.

genomics↗

bioRxiv2023

Patterns of physical activity in hunter-gatherer children compared with US and UK children.

Sedentary lifestyles, mismatched with our active foraging history, contribute to escalating rates of non-communicable diseases. Contemporary hunter-gatherers appear to be highly active, but little is known about physical activity levels in hunter-gatherer children. We analysed 150 days of accelerometer data from 51 BaYaka hunter-gatherer children (aged 3-18) in the Republic of Congo, comparing it with British and American children (MCS and NHANES). BaYaka children were highly active, engaging in over 3 hours of moderate-to-vigorous physical activity (MVPA) daily, surpassing British adolescents by over 70 minutes. In US children activity declined with age; while in BaYaka children activity increased with age, unaffected by gender. Reflecting their foraging lifestyle, activity patterns varied within and between days, yet all children consistently rose with the sun. These findings highlight the impact of a foraging upbringing on childrens activity levels, providing a benchmark for understanding childhood physical activity and wellbeing.

evolutionary biology↗

bioRxiv2021

Genetic nurture effects on education: a systematic review and meta-analysis

Child educational development is associated with major psychological, social, economic and health milestones throughout the life course. Understanding the early origins of educational inequalities and their reproduction across generations is therefore crucial. Recent genomic studies provide novel insights in this regard, uncovering "genetic nurture" effects, whereby parental genotypes influence offsprings educational development via environmental pathways rather than genetic transmission. These findings have yet to be systematically appraised. We conducted the first systematic review and meta-analysis to quantify genetic nurture effects on educational outcomes and investigate key moderators. Twelve studies comprising 38,654 distinct parent(s)-offspring pairs or trios from eight cohorts were included, from which we derived 22 estimates of genetic nurture effects. Multilevel random effects models showed that the effect of genetic nurture on offsprings educational outcomes ({beta}genetic nurture = 0.08, 95% CI [0.07, 0.09]) was about half the size of direct genetic effects ({beta}direct genetic = 0.17, 95% CI [0.13, 0.20]). Maternal and paternal genetic nurture effects were similar in magnitude, suggesting comparable roles of mothers and fathers in determining their childrens educational outcomes. Genetic nurture effects were largely explained by parental educational level and family socioeconomic status, suggesting that genetically influenced environments play an important role in shaping child educational outcomes. Even after accounting for genetic transmission, we provide evidence that environmentally mediated parental genetic influences contribute to the intergenerational transmission of educational outcomes. Further exploring these downstream environmental pathways may inform educational policies aiming to break the intergenerational cycle of educational underachievement and foster social mobility. Public Significance StatementThis meta-analysis demonstrates that parents genetics influence their childrens educational outcomes through the rearing environments that parents provide. This "genetic nurture" effect is largely explained by family socioeconomic status and parental education level, is similar for mothers and fathers (suggesting that both parents equally shape their childrens educational outcomes) and is about half the size of direct genetic effects on childrens educational outcomes. Interventions targeting such environmental pathways could help to break the intergenerational cycle of educational underachievement and foster social mobility.

genetics↗

bioRxiv2019

An Integrated Framework for Genome Analysis Reveals Numerous Previously Unrecognizable Structural Variants in Leukemia Patients' Samples

While genomic analysis of tumors has stimulated major advances in cancer diagnosis, prognosis and treatment, current methods fail to identify a large fraction of somatic structural variants in tumors. We have applied a combination of whole genome sequencing and optical genome mapping to a number of adult and pediatric leukemia samples, which revealed in each of these samples a large number of structural variants not recognizable by current tools of genomic analyses. We developed computational methods to determine which of those variants likely arose as somatic mutations. The method identified 97% of the structural variants previously reported by karyotype analysis of these samples and revealed an additional fivefold more such somatic rearrangements. The method identified on average tens of previously unrecognizable inversions and duplications and hundreds of previously unrecognizable insertions and deletions. These structural variants recurrently affected a number of leukemia associated genes as well as cancer driver genes not previously associated with leukemia and genes not previously associated with cancer. A number of variants only affected intergenic regions but caused cis-acting alterations in expression of neighboring genes. Analysis of TCGA data indicates that the status of several of the recurrently mutated genes identified in this study significantly affect survival of AML patients. Our results suggest that current genomic analysis methods fail to identify a majority of structural variants in leukemia samples and this lacunae may hamper diagnostic and prognostic efforts.

genomics↗

bioRxiv2019

Determinants of the population health distribution, or why are risk factor-body mass index associations larger at the upper end of the BMI distribution?

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression) -associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in a single dataset (the 1958 British birth cohort study). Associations of low childhood socioeconomic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socioeconomic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th-90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss possible research and policy implications. We conclude by stating that tools such as quantile regression may be useful to better understand how risk factors relate to the distribution of health -particularly so in obesity research given conventional reliance on cut-points -yet for other outcomes in addition given the continuous nature of population health.

epidemiology↗

bioRxiv2018

Physical activity in adolescence: cross-national comparisons of levels, distributions and disparities across 52 countries

IntroductionDespite global concerns regarding physical inactivity, limited cross-national evidence exists to compare adolescents physical activity participation. We analysed 52 high- and low-middle income countries, with activity undertaken inside and outside of school in 2015. We investigated gender- and socioeconomic-disparities, and additionally examined correlations with country-level indices of physical education (PE) curriculum time allocation, wealth, and income inequality.\n\nMethodsWe used the Programme for International Student Assessment (PISA), a nationally representative cross-sectional survey of 15-year-olds (N=347,935). Students reported average attendance (days/week) in PE classes, and the days/week engaged in moderate activity (MPA) and vigorous activity (VPA) outside of school. Both the mean and distributions of outcomes were evaluated, as were gender- and socioeconomic-disparities. Pearsons correlations (r) between the physical activity outcomes and PE curriculum time allocation, wealth (indexed by GDP) and income inequality (indexed by the Gini coefficient) were calculated.\n\nResultsActivity levels inside and outside of school were higher in Eastern Europe than Western Europe, the Americas, and the Middle East/North Africa. Comparisons of average levels masked potentially important differences in distributions. For example, activity levels inside school showed a bimodal distribution in the US (mean PE class attendance 2.4 days/week; 41.3%, 6.3% and 33.1% of students attended PE classes on 0, 2 and 5 days/week respectively). In contrast, most other countries exhibited more centrally shaped distributions. Pro-male and pro-high socioeconomic disparities were modest for participation inside school, but higher for MPA and VPA outside of school. The magnitude of these also differed markedly by country. Activity in school was weakly positively correlated with PE curriculum time allocation (r=0.33); activity outside of school was strongly negatively correlated with income inequality (e.g. r=-0.69 for MPA).\n\nConclusionOur findings reveal extensive cross-country differences in adolescents physical activity; in turn, these highlight policy areas that could ultimately improve global adolescent health, such as the incorporation of minimum country-level PE classes, and the targeting of gender- and socioeconomic- disparities in activity conducted outside of school. Our findings also highlight the utility of educational databases such as PISA for use in global population health research.

epidemiology↗