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Article ; Online: The association between cognitive ability and body mass index

Liam Wright / Neil M. Davies / David Bann

PLoS Medicine, Vol 20, Iss

A sibling-comparison analysis in four longitudinal studies

2023 Volume 4

Abstract: Background Body mass index (BMI) and obesity rates have increased sharply since the 1980s. While multiple epidemiologic studies have found that higher adolescent cognitive ability is associated with lower adult BMI, residual and unobserved confounding ... ...

Abstract	Background Body mass index (BMI) and obesity rates have increased sharply since the 1980s. While multiple epidemiologic studies have found that higher adolescent cognitive ability is associated with lower adult BMI, residual and unobserved confounding due to family background may explain these associations. We used a sibling design to test this association accounting for confounding factors shared within households. Methods and findings We used data from four United States general youth population cohort studies: the National Longitudinal Study of Youth 1979 (NLSY-79), the NLSY-79 Children and Young Adult, the NLSY 1997 (NLSY-97), and the Wisconsin Longitudinal Study (WLS); a total of 12,250 siblings from 5,602 households followed from adolescence up to age 62. We used random effects within-between (REWB) and residualized quantile regression (RQR) models to compare between- and within-family estimates of the association between adolescent cognitive ability and adult BMI (20 to 64 years). In REWB models, moving from the 25th to 75th percentile of adolescent cognitive ability was associated with −0.95 kg/m2 (95% CI = −1.21, −0.69) lower BMI between families. Adjusting for family socioeconomic position reduced the association to −0.61 kg/m2 (−0.90, −0.33). However, within families, the association was just −0.06 kg/m2 (−0.35, 0.23). This pattern of results was found across multiple specifications, including analyses conducted in separate cohorts, models examining age-differences in association, and in RQR models examining the association across the distribution of BMI. Limitations include the possibility that within-family estimates are biased due to measurement error of the exposure, confounding via non-shared factors, and carryover effects. Conclusions The association between high adolescent cognitive ability and low adult BMI was substantially smaller in within-family compared with between-family analysis. The well-replicated associations between cognitive ability and subsequent BMI may largely reflect ...
Keywords	Medicine ; R
Subject code	796
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The association between cognitive ability and body mass index

Liam Wright / Neil M Davies / David Bann

PLoS Medicine, Vol 20, Iss 4, p e

A sibling-comparison analysis in four longitudinal studies.

2023 Volume 1004207

Abstract	Background Body mass index (BMI) and obesity rates have increased sharply since the 1980s. While multiple epidemiologic studies have found that higher adolescent cognitive ability is associated with lower adult BMI, residual and unobserved confounding due to family background may explain these associations. We used a sibling design to test this association accounting for confounding factors shared within households. Methods and findings We used data from four United States general youth population cohort studies: the National Longitudinal Study of Youth 1979 (NLSY-79), the NLSY-79 Children and Young Adult, the NLSY 1997 (NLSY-97), and the Wisconsin Longitudinal Study (WLS); a total of 12,250 siblings from 5,602 households followed from adolescence up to age 62. We used random effects within-between (REWB) and residualized quantile regression (RQR) models to compare between- and within-family estimates of the association between adolescent cognitive ability and adult BMI (20 to 64 years). In REWB models, moving from the 25th to 75th percentile of adolescent cognitive ability was associated with -0.95 kg/m2 (95% CI = -1.21, -0.69) lower BMI between families. Adjusting for family socioeconomic position reduced the association to -0.61 kg/m2 (-0.90, -0.33). However, within families, the association was just -0.06 kg/m2 (-0.35, 0.23). This pattern of results was found across multiple specifications, including analyses conducted in separate cohorts, models examining age-differences in association, and in RQR models examining the association across the distribution of BMI. Limitations include the possibility that within-family estimates are biased due to measurement error of the exposure, confounding via non-shared factors, and carryover effects. Conclusions The association between high adolescent cognitive ability and low adult BMI was substantially smaller in within-family compared with between-family analysis. The well-replicated associations between cognitive ability and subsequent BMI may largely reflect ...
Keywords	Medicine ; R
Subject code	796
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Weakening of the cognition and height association from 1957 to 2018

David Bann / Liam Wright / Neil M Davies / Vanessa Moulton

eLife, Vol

Findings from four British birth cohort studies

2023 Volume 12

Abstract: Background: Taller individuals have been repeatedly found to have higher scores on cognitive assessments. Recent studies have suggested that this association can be explained by genetic factors, yet this does not preclude the influence of environmental ... ...

Abstract	Background: Taller individuals have been repeatedly found to have higher scores on cognitive assessments. Recent studies have suggested that this association can be explained by genetic factors, yet this does not preclude the influence of environmental or social factors that may change over time. We thus tested whether the association changed across time using data from four British birth cohorts (born in 1946, 1958, 1970, and 2001). Methods: In each cohort height was measured and cognition via verbal reasoning, vocabulary/comprehension, and mathematical tests; at ages 10/11 and 14/17 years (N=41,418). We examined associations between height and cognition at each age, separately in each cohort, and for each cognitive test administered. Linear and quantile regression models were used. Results: Taller participants had higher mean cognitive assessment scores in childhood and adolescence, yet the associations were weaker in later (1970 and 2001) cohorts. For example, the mean difference in height comparing the highest with lowest verbal cognition scores at 10/11 years was 0.57 SD (95% CI = 0.44–0.70) in the 1946 cohort, yet 0.30 SD (0.23–0.37) in the 2001 cohort. Expressed alternatively, there was a reduction in correlation from 0.17 (0.15–0.20) to 0.08 (0.06–0.10). This pattern of change in the association was observed across all ages and cognition measures used, was robust to adjustment for social class and parental height, and modeling of plausible missing-not-at-random scenarios. Quantile regression analyses suggested that these differences were driven by differences in the lower centiles of height, where environmental influence may be greatest. Conclusions: Associations between height and cognitive assessment scores in childhood-adolescence substantially weakened from 1957–2018. These results support the notion that environmental and social change can markedly weaken associations between cognition and other traits. Funding: DB is supported by the Economic and Social Research Council (grant number ES/M001660/1); ...
Keywords	height ; cognitive function ; intelligence ; cross-cohort ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	333
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Investigating how the accuracy of teacher expectations of pupil performance relate to socioeconomic and genetic factors

Ciarrah-Jane Shannon Barry / Neil M. Davies / Tim T. Morris

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract Teacher expectations of pupil ability can influence educational progression, impacting subsequent streaming and exam level. Systematic discrepancies between teacher expectations of pupil achievement may therefore have a detrimental effect on ... ...

Abstract	Abstract Teacher expectations of pupil ability can influence educational progression, impacting subsequent streaming and exam level. Systematic discrepancies between teacher expectations of pupil achievement may therefore have a detrimental effect on children’s education. Associations between socioeconomic and demographic factors with teacher expectation accuracy have been demonstrated, but it is not known how teacher expectations of achievement may relate to genetic factors. We investigated these relationships using nationally standardized exam results at ages 11 and 14 from a UK longitudinal cohort study. We found that teacher expectation of achievement was strongly correlated with educational test scores. Furthermore, the accuracy of teacher expectation was patterned by pupil socioeconomic background but not teacher characteristics. The accuracy of teacher expectation related to pupil’s genetic liability to education as captured by a polygenic score for educational attainment. Despite correlation with the polygenic score, we found no strong evidence for genomewide SNP heritability in teacher reporting accuracy.
Keywords	Medicine ; R ; Science ; Q
Subject code	370
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Little genomic support for Cyclophilin A-matrix metalloproteinase-9 pathway as a therapeutic target for cognitive impairment in APOE4 carriers

Emma L. Anderson / Dylan M. Williams / Venexia M. Walker / Neil M. Davies

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 6

Abstract: Abstract Therapeutic targets for halting the progression of Alzheimer’s disease pathology are lacking. Recent evidence suggests that APOE4, but not APOE3, activates the Cyclophilin-A matrix metalloproteinase-9 (CypA-MMP9) pathway, leading to an ... ...

Abstract	Abstract Therapeutic targets for halting the progression of Alzheimer’s disease pathology are lacking. Recent evidence suggests that APOE4, but not APOE3, activates the Cyclophilin-A matrix metalloproteinase-9 (CypA-MMP9) pathway, leading to an accelerated breakdown of the blood–brain barrier (BBB) and thereby causing neuronal and synaptic dysfunction. Furthermore, blockade of the CypA-MMP9 pathway in APOE4 knock-in mice restores BBB integrity and subsequently normalizes neuronal and synaptic function. Thus, CypA has been suggested as a potential target for treating APOE4 mediated neurovascular injury and the resulting neuronal dysfunction and degeneration. The odds of drug targets passing through clinical trials are greatly increased if they are supported by genomic evidence. We found little evidence to suggest that CypA or MMP9 affects the risk of Alzheimer’s disease or cognitive impairment using two-sample Mendelian randomization and polygenic risk score analysis in humans. This casts doubt on whether they are likely to represent effective drug targets for cognitive impairment in human APOE4 carriers.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Can education be personalised using pupils’ genetic data?

Tim T Morris / Neil M Davies / George Davey Smith

eLife, Vol

2020 Volume 9

Abstract: The increasing predictive power of polygenic scores for education has led to their promotion by some as a potential tool for genetically informed policy. How accurately polygenic scores predict an individual pupil's educational performance conditional on ...

Abstract	The increasing predictive power of polygenic scores for education has led to their promotion by some as a potential tool for genetically informed policy. How accurately polygenic scores predict an individual pupil's educational performance conditional on other phenotypic data is however not well understood. Using data from a UK cohort study with data linkage to national schooling records, we investigated how accurately polygenic scores for education predicted pupils’ test score achievement. We also assessed the performance of polygenic scores over and above phenotypic data that are available to schools. Across our sample, there was high overlap between the polygenic score and achievement distributions, leading to poor predictive accuracy at the individual level. Prediction of educational outcomes from polygenic scores were inferior to those from parental socioeconomic factors. Conditional on prior achievement, polygenic scores failed to accurately predict later achievement. Our results suggest that while polygenic scores can be informative for identifying group level differences, they currently have limited use for accurately predicting individual educational performance or for personalised education.
Keywords	genetics ; education ; prediction ; polygenic score ; achievement ; ALSPAC ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Causal effect of children’s secondary education on parental health outcomes

Neil M Davies / Jacob Bor / Jan-Walter De Neve / Jan Ole Ludwig

BMJ Open, Vol 11, Iss

findings from a natural experiment in Botswana

2021 Volume 1

Abstract: Objectives A growing literature highlights the intergenerational transmission of human capital from parents to children. However, far less is known about ‘upward transmission’ from children to parents. In this study, we use a 1996 Botswana education ... ...

Abstract	Objectives A growing literature highlights the intergenerational transmission of human capital from parents to children. However, far less is known about ‘upward transmission’ from children to parents. In this study, we use a 1996 Botswana education policy reform as a natural experiment to identify the causal effect of children’s secondary schooling on their parents’ health.Setting Botswana’s decennial census (2001 and 2011). Data were obtained through the Integrated Public Use Microdata Series and are 10% random samples of the complete population in each of these census years.Participants Survey respondents who were citizens born in Botswana, at least 18 years old at the time of the census and born in or after 1975 (n=89 721).Primary and secondary outcome measures Parental survival and disability at the time of the census, separately for mothers and fathers.Results The 1996 reform caused a large increase in grade 10 enrolment, inducing an additional 0.4 years of schooling for the first cohorts affected (95% CI 0.3 to 0.5, p<0.001). The reform, however, had no effect on parental survival and disability by the time exposed child cohorts reach age 30. Results were robust to a wide array of sensitivity analyses.Conclusions This study found little evidence that parents’ survival and disability were affected by their offspring’s educational attainment in Botswana. Parents’ health may not be necessarily affected by increasing their offspring’s educational attainment.
Keywords	Medicine ; R
Subject code	360
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term cost-effectiveness of interventions for obesity

Sean Harrison / Padraig Dixon / Hayley E Jones / Alisha R Davies / Laura D Howe / Neil M Davies

PLoS Medicine, Vol 18, Iss 8, p e

A mendelian randomisation study.

2021 Volume 1003725

Abstract: Background The prevalence of obesity has increased in the United Kingdom, and reliably measuring the impact on quality of life and the total healthcare cost from obesity is key to informing the cost-effectiveness of interventions that target obesity, and ...

Abstract	Background The prevalence of obesity has increased in the United Kingdom, and reliably measuring the impact on quality of life and the total healthcare cost from obesity is key to informing the cost-effectiveness of interventions that target obesity, and determining healthcare funding. Current methods for estimating cost-effectiveness of interventions for obesity may be subject to confounding and reverse causation. The aim of this study is to apply a new approach using mendelian randomisation for estimating the cost-effectiveness of interventions that target body mass index (BMI), which may be less affected by confounding and reverse causation than previous approaches. Methods and findings We estimated health-related quality-adjusted life years (QALYs) and both primary and secondary healthcare costs for 310,913 men and women of white British ancestry aged between 39 and 72 years in UK Biobank between recruitment (2006 to 2010) and 31 March 2017. We then estimated the causal effect of differences in BMI on QALYs and total healthcare costs using mendelian randomisation. For this, we used instrumental variable regression with a polygenic risk score (PRS) for BMI, derived using a genome-wide association study (GWAS) of BMI, with age, sex, recruitment centre, and 40 genetic principal components as covariables to estimate the effect of a unit increase in BMI on QALYs and total healthcare costs. Finally, we used simulations to estimate the likely effect on BMI of policy relevant interventions for BMI, then used the mendelian randomisation estimates to estimate the cost-effectiveness of these interventions. A unit increase in BMI decreased QALYs by 0.65% of a QALY (95% confidence interval [CI]: 0.49% to 0.81%) per year and increased annual total healthcare costs by £42.23 (95% CI: £32.95 to £51.51) per person. When considering only health conditions usually considered in previous cost-effectiveness modelling studies (cancer, cardiovascular disease, cerebrovascular disease, and type 2 diabetes), we estimated that a unit ...
Keywords	Medicine ; R
Subject code	360
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The causes and consequences of Alzheimer’s disease

Roxanna Korologou-Linden / Laxmi Bhatta / Ben M. Brumpton / Laura D. Howe / Louise A. C. Millard / Katarina Kolaric / Yoav Ben-Shlomo / Dylan M. Williams / George Davey Smith / Emma L. Anderson / Evie Stergiakouli / Neil M. Davies

Nature Communications, Vol 13, Iss 1, Pp 1-

phenome-wide evidence from Mendelian randomization

2022 Volume 14

Abstract: Observational studies have found overlap between Alzheimer’s disease and other diseases and phenotypes, although the causal relationships are unclear. Here, the authors perform an age-stratified phenome-wide association study of Alzheimer’s disease (AD) ... ...

Abstract	Observational studies have found overlap between Alzheimer’s disease and other diseases and phenotypes, although the causal relationships are unclear. Here, the authors perform an age-stratified phenome-wide association study of Alzheimer’s disease (AD) genetic liability and follow-up Mendelian randomization analyses to examine whether these phenotypes have a causal effect on AD.
Keywords	Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetic evidence for assortative mating on alcohol consumption in the UK Biobank

Laurence J. Howe / Daniel J. Lawson / Neil M. Davies / Beate St. Pourcain / Sarah J. Lewis / George Davey Smith / Gibran Hemani

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 10

Abstract: From observational studies, alcohol consumption behaviours are known to be correlated in spouses. Here, Howe et al. use partners’ genotypic information in a Mendelian randomization framework and show that a SNP in the ADH1B gene associates with partner’s ...

Abstract	From observational studies, alcohol consumption behaviours are known to be correlated in spouses. Here, Howe et al. use partners’ genotypic information in a Mendelian randomization framework and show that a SNP in the ADH1B gene associates with partner’s alcohol consumption, suggesting that alcohol consumption affects mate choice.
Keywords	Science ; Q
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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