Demographic, socioeconomic and life-course risk factors for internalized weight stigma in adulthood: evidence from an English birth cohort study.

Background: Obesity is highly stigmatized, with negative obesity-related stereotypes widespread across society. Internalized weight stigma (IWS) is linked to negative outcomes including poor mental health and disordered eating. Previous evidence examining population groups at higher risk of experiencing IWS comes from small, nonrepresentative samples. Here, we re-assess previously reported associations of IWS with demographic, socioeconomic, and wider social factors in a large general population birth cohort study for the first time. Methods: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we explored differences in IWS at age 31 years by sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences, using confounder-adjusted multivariable regression. Findings: In models adjusted for potential confounders and BMI in childhood, adolescence, and adulthood (N = 4060), IWS was higher for females (standardized beta: 0.56, 95% CI: 0.50, 0.61), sexual minorities (0.17 S.D. higher, 95% CI: 0.09, 0.24), and less socioeconomically advantaged individuals (e.g., 0.16 S.D. higher (95% CI: 0.08, 0.24) for participants whose mothers had minimum or no qualifications, compared to a university degree). The social environment during adolescence and young adulthood was important: IWS was higher for people who at age 13 years felt pressure to lose weight from family (by 0.13 S.D., 95% CI: 0.03, 0.23), and the media (by 0.17, 95% CI: 0.10, 0.25), or had experienced bullying (e.g., 0.25 S.D., 95% CI: 0.17, 0.33 for bullying at age 23 years). Interpretation: Internalized weight stigma differs substantially between demographic groups. Risk is elevated for females, sexual minorities, and socioeconomically disadvantaged adults, and this is not explained by differences in BMI. Pressure to lose weight from family and the media in adolescence may have long-lasting effects on IWS. Funding: The ESRC, MRC, NIHR, and Wellcome Trust.

The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self-harm and depression: findings from three UK prospective population-based cohorts.

BACKGROUND: Adverse childhood experiences (ACEs) are well-established risk factors for self-harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co-occurring self-harm and depression. METHODS: Data were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14-18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E-Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four-category outcome: no self-harm or depression, self-harm alone, depression alone and self-harm with co-occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self-harm and depression in adolescence. RESULTS: The majority of ACEs were associated with co-occurring self-harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co-occurring self-harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10-1.25) and MCS (1.18, 1.11-1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co-occurring self-harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS. CONCLUSIONS: Efforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long-term exposure to ACEs contributing to risk of self-harm and depression in adolescence.

Genetics impact risk of Alzheimer's disease through mechanisms modulating structural brain morphology in late life.

BACKGROUND: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively. METHODS: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank). We also examined the effects of global and regional cortical thickness and subcortical volumes from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium on AD risk in up to 37 741 participants. RESULTS: Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. Some of the identified structures are not typically implicated in AD, such as those in the striatum (eg, thalamus), with consistent effects from childhood to late adulthood. There was little evidence to suggest brain morphology alters AD risk. CONCLUSIONS: Genetic liability to AD is likely to affect risk of AD primarily through mechanisms affecting indicators of brain morphology in later life, rather than structural brain reserve. Future studies with repeated measures are required for a better understanding and certainty of the mechanisms at play.

Differences between brachial and aortic blood pressure in adolescence and their implications for diagnosis of hypertension.

OBJECTIVES: Blood pressure (BP) is the leading global cause of mortality, and its prevalence is increasing in children and adolescents. Aortic BP is lower than brachial BP in adults. We aimed to assess the extent of this difference and its impact on the diagnosis of hypertension among adolescents. METHODS: We used data from 3850 participants from a UK cohort of births in the early 1990s in the Southwest of England, who attended their ∼17-year follow-up and had valid measures of brachial and aortic BP at that clinic [mean (SD) age 17.8 (0.4) years, 66% female individuals]. Data are presented as mean differences [95% prediction intervals] for both sexes. RESULTS: Aortic systolic BP (SBP) was lower than brachial SBP [male, -22.3 (-31.2, -13.3) mmHg; female, -17.8 (-25.5, -10.0) mmHg]. Differences between aortic and brachial diastolic BP (DBP) were minimal. Based on brachial BP measurements, 101 male individuals (6%) and 22 female individuals (1%) were classified as hypertensive. In contrast, only nine male individuals (<1%) and 14 female individuals (<1%) met the criteria for hypertension based on aortic BP, and the predictive value of brachial BP for aortic hypertension was poor (positive-predictive value = 13.8%). Participants with aortic hypertension had a higher left ventricular mass index than those with brachial hypertension. CONCLUSION: Brachial BP substantially overestimates aortic BP in adolescents because of marked aortic-to-brachial pulse pressure amplification. The use of brachial BP measurement may result in an overdiagnosis of hypertension during screening in adolescence.

Mendelian Randomization analysis of the causal effect of cigarette smoking on hospital costs.

INTRODUCTION: Knowledge of the impact of smoking on healthcare costs is important for establishing the external effects of smoking and for evaluating policies intended to modify this behavior. Conventional analysis of this association is difficult because of omitted variable bias, reverse causality, and measurement error. METHODS: We approached these challenges using a Mendelian Randomization study design; genetic variants associated with smoking behaviors were used in instrumental variables models with inpatient hospital costs (calculated from electronic health records) as the outcome. We undertook genome wide association studies to identify genetic variants associated with smoking initiation and a composite smoking index (reflecting cumulative health impacts of smoking) on up to 300,045 individuals (mean age: 57 years at baseline, range 39 to 72 years) in the UK Biobank. We followed individuals up for a mean of six years. RESULTS: Genetic liability to initiate smoking (ever versus never smoking) was estimated to increase mean per-patient annual inpatient hospital costs by £477 (95% confidence interval (CI): £187 to £766). A one-unit change in genetic liability to the composite smoking index (range: 0-4.0) increased inpatient hospital costs by £204 (95% CI: £105 to £303) per unit increase in this index. There was some evidence that the composite smoking index causal models violated the instrumental variable assumptions, and all Mendelian Randomization models were estimated with considerable uncertainty. Models conditioning on risk tolerance were not robust to weak instrument bias. CONCLUSIONS: Our findings have implications for the potential cost-effectiveness of smoking interventions. IMPLICATIONS: We report the first Mendelian Randomization analysis of the causal effect of smoking on healthcare costs. Using two distinct smoking phenotypes, we identified substantial impacts of smoking on inpatient hospital costs, although the causal models were associated with considerable uncertainty. These results could be used alongside other evidence on the impact of smoking to evaluate the cost-effectiveness of anti-smoking interventions and to understand the scale of externalities associated with this behaviour.

Infection and telomere length: a systematic review protocol.

INTRODUCTION: Telomeres are a measure of cellular ageing with potential links to diseases such as cardiovascular diseases and cancer. Studies have shown that some infections may be associated with telomere shortening, but whether an association exists across all types and severities of infections and in which populations is unclear. Therefore we aim to collate available evidence to enable comparison and to inform future research in this field. METHODS AND ANALYSIS: We will search for studies involving telomere length and infection in various databases including MEDLINE (Ovid interface), EMBASE (Ovid interface), Web of Science, Scopus, Global Health and the Cochrane Library. For grey literature, the British Library of electronic theses databases (ETHOS) will be explored. We will not limit by study type, geographical location, infection type or method of outcome measurement. Two researchers will independently carry out study selection, data extraction and risk of bias assessment using the ROB2 and ROBINS-E tools. The overall quality of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation criteria. We will also evaluate study heterogeneity with respect to study design, exposure and outcome measurement and if there is sufficient homogeneity, a meta-analysis will be conducted. Otherwise, we will provide a narrative synthesis with results grouped by exposure category and study design. ETHICS AND DISSEMINATION: The present study does not require ethical approval. Results will be disseminated via publishing in a peer-reviewed journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023444854.

Maternal depressive symptoms and young people's higher education participation and choice of university: Evidence from a longitudinal cohort study.

BACKGROUND: Participation in higher education has significant and long-lasting consequences for people's socioeconomic trajectories. Maternal depression is linked to poorer educational achievement for children in school, but its impact on university attendance is unclear. METHODS: In an English longitudinal cohort study (N = 8952), we explore whether young people whose mothers experienced elevated depressive symptoms are less likely to attend university, and the role of potential mediators in the young person: educational achievement in school, depressive symptoms, and locus of control. We also examine whether maternal depressive symptoms influence young people's choice of university, and non-attendees' reasons for not participating in higher education. RESULTS: Young people whose mothers experienced more recurrent depressive symptoms were less likely to attend university (OR = 0.88, CI = 0.82,0.94, p < 0.001) per occasion of elevated maternal depressive symptoms) after adjusting for confounders. Mediation analysis indicated this was largely explained by educational achievement in school (e.g., 82.7 % mediated by age 16 achievement) and locus of control at 16. There was mixed evidence for an impact on choice of university. For participants who did not study at university, maternal depressive symptoms were linked to stating as a reason having had other priorities to do with family or children (OR: 1.17, CI = 1.02,1.35). LIMITATIONS: Lack of data on the other parent's depression, loss to follow-up, possibly selective non-response. CONCLUSIONS: Young people whose mothers experience elevated depressive symptoms on multiple occasions are less likely to participate in higher education; educational achievement in secondary school, but not the young people's own depressive symptoms, substantially mediated the effect.

Menstrual cycle features in mothers and daughters in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Problematic menstrual cycle features, including irregular periods, severe pain, heavy bleeding, absence of periods, frequent or infrequent cycles, and premenstrual symptoms, are experienced by high proportions of females and can have substantial impacts on their health and well-being. However, research aimed at identifying causes and risk factors associated with such menstrual cycle features is sparse and limited. This data note describes prospective, longitudinal data collected in a UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), on menstrual cycle features, which can be utilised to address the research gaps in this area. Data were collected across 21 timepoints (between the average age of 28.6 and 57.7 years) in mothers (G0) and 20 timepoints (between the average age of 8 and 24 years) in index daughters (G1) between 1991 and 2020. This data note details all available variables, proposes methods to derive comparable variables across data collection timepoints, and discusses important limitations specific to each menstrual cycle feature. Also, the data note identifies broader issues for researchers to consider when utilising the menstrual cycle feature data, such as hormonal contraception, pregnancy, breastfeeding, and menopause, as well as missing data and misclassification.

The bidirectional effects between cognitive ability and brain morphology: A life course Mendelian randomization analysis.

Introduction: Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area. Methods: Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864). Analyses were stratified for developmental periods (childhood, early adulthood, mid-to-late adulthood; age range: 8-81 years). Results: The earliest effects were observed in childhood and early adulthood in the frontoparietal lobes. A bidirectional relationship was identified between higher cognitive ability, larger estimated total intracranial volume (childhood, mid-to-late adulthood) and total surface area (all life stages). A thicker posterior cingulate cortex and a larger surface area in the caudal middle frontal cortex and temporal pole were associated with greater cognitive ability. Contrary, a thicker temporal pole was associated with lower cognitive ability. Discussion: Stable effects of cognitive ability on brain morphology across the life course suggests that childhood is potentially an important window for intervention.

Childhood socioeconomic position and sex-specific trajectories of metabolic traits across early life: prospective cohort study.

BACKGROUND: Socioeconomic inequalities in cardiovascular disease risk begin early in life and are more pronounced in females than males later in life. Causal atherogenic traits explaining this are not well understood. We explored sex-specific associations between childhood socioeconomic position (SEP) and molecular measures of systemic metabolism across early life. METHODS: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort in southwest England. Pregnant women with an expected delivery date between 1991 and 1992 were invited to participate. Maternal education was the primary indicator of SEP. Concentrations of 148 metabolic traits from targeted metabolomics (nuclear magnetic resonance spectroscopy) from research clinics at ages 7, 15, 18 and 25 years were analysed. The sex-specific slope index of inequality (SII) in trajectories of metabolic traits was estimated using multilevel models. FINDINGS: Total number of participants included was 6537 (12,543 repeated measures). Lower maternal education was associated with more adverse levels of several atherogenic lipids and key metabolic traits among females at age 7 years, but not males. For instance, SII for very small very-low-density lipoprotein (VLDL) concentrations was 0.16SD (95% CI: 0.01, 0.30) among females and -0.02SD (95% CI: -0.16, 0.13) among males. Between 7 and 25 years, inequalities widened among females and emerged among males particularly for VLDL particle concentrations, apolipoprotein-B concentrations, and inflammatory glycoprotein acetyls. For instance, at 25 years, SII for very small VLDL concentrations was 0.36SD (95% CI: 0.20, 0.52) and 0.22SD (95% CI: 0.04, 0.40) among females and males respectively. INTERPRETATION: Prevention of socioeconomic inequalities in cardiovascular disease risk requires a life course approach beginning at the earliest opportunity, especially among females. FUNDING: The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). KON is supported by a Health Research Board (HRB) of Ireland Investigator Led Award (ILP-PHR-2022-008). JB, GDS and KT work in a unit funded by the UK MRC (MC_UU_00011/1 and MC UU 00011/3) and the University of Bristol. OR is supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). These funding sources had no role in the design and conduct of this study. This publication is the work of the authors and KON will serve as guarantor for the contents of this paper.

Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.

Diseases diagnosed in adulthood may have antecedents throughout (including prenatal) life. Gaining a better understanding of how exposures at different stages in the lifecourse influence health outcomes is key to elucidating the potential benefits of disease prevention strategies. Mendelian randomisation (MR) is increasingly used to estimate causal effects of exposures across the lifecourse on later life outcomes. This systematic literature review explores MR methods used to perform lifecourse investigations and reviews previous work that has utilised MR to elucidate the effects of factors acting at different stages of the lifecourse. We conducted searches in PubMed, Embase, Medline and MedRXiv databases. Thirteen methodological studies were identified. Four studies focused on the impact of time-varying exposures in the interpretation of "standard" MR techniques, five presented methods for repeat measures of the same exposure, and four described methodological approaches to handling multigenerational exposures. A further 127 studies presented the results of an applied research question. Over half of these estimated effects in a single generation and were largely confined to the exploration of questions regarding body composition. The remaining mostly estimated maternal effects. There is a growing body of research focused on the development and application of MR methods to address lifecourse research questions. The underlying assumptions require careful consideration and the interpretation of results rely on select conditions. Whilst we do not advocate for a particular strategy, we encourage practitioners to make informed decisions on how to approach a research question in this field with a solid understanding of the limitations present and how these may be affected by the research question, modelling approach, instrument selection, and data availability.

Time-sensitive testing pressures and COVID-19 outcomes: are socioeconomic inequalities over the first year of the pandemic explained by selection bias?

BACKGROUND: There are many ways in which selection bias might impact COVID-19 research. Here we focus on selection for receiving a polymerase-chain-reaction (PCR) SARS-CoV-2 test and how known changes to selection pressures over time may bias research into COVID-19 infection. METHODS: Using UK Biobank (N = 420,231; 55% female; mean age = 66.8 [SD = 8·11]) we estimate the association between socio-economic position (SEP) and (i) being tested for SARS-CoV-2 infection versus not being tested (ii) testing positive for SARS-CoV-2 infection versus testing negative and (iii) testing negative for SARS-CoV-2 infection versus not being tested. We construct four distinct time-periods between March 2020 and March 2021, representing distinct periods of testing pressures and lockdown restrictions and specify both time-stratified and combined models for each outcome. We explore potential selection bias by examining associations with positive and negative control exposures. RESULTS: The association between more disadvantaged SEP and receiving a SARS-CoV-2 test attenuated over time. Compared to individuals with a degree, individuals whose highest educational qualification was a GCSE or equivalent had an OR of 1·27 (95% CI: 1·18 to 1·37) in March-May 2020 and 1·13 (95% CI: 1.·10 to 1·16) in January-March 2021. The magnitude of the association between educational attainment and testing positive for SARS-CoV-2 infection increased over the same period. For the equivalent comparison, the OR for testing positive increased from 1·25 (95% CI: 1·04 to 1·47), to 1·69 (95% CI: 1·55 to 1·83). We found little evidence of an association between control exposures, and any considered outcome. CONCLUSIONS: The association between SEP and SARS-CoV-2 testing changed over time, highlighting the potential of time-specific selection pressures to bias analyses of COVID-19. Positive and negative control analyses suggest that changes in the association between SEP and SARS-CoV-2 infection over time likely reflect true increases in socioeconomic inequalities.

Early-life socioeconomic circumstances and the comorbidity of depression and overweight in adolescence and young adulthood: A prospective study.

Depression and overweight both often emerge early in life and have been found to be associated, but few studies examine depression-overweight comorbidity and its social patterning early in the life course. Drawing on data from 4,948 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort from the UK (2,798 female, 2,150 male), we investigated how different aspects of early-life socioeconomic circumstances are associated with depression-overweight comorbidity from adolescence to young adulthood exploring any differences by age and sex. We estimated how parental education, social class and financial difficulties reported in pregnancy were associated with depression and overweight, and their comorbidity at approximately the ages 17 and 24 in males and females. The results from multinomial logistic regression models showed that all three socioeconomic markers were associated with depression-overweight comorbidity and results were similar across age. Lower parental education (relative risk ratio (RRR) and 95% confidence interval (CI) of low education v high education: 3.61 (2.30-5.67) in females and 1.54 (1.14-2.07) in males) and social class (class IV/V v class I: 5.67 (2.48-12.94) in females and 3.11 (0.70-13.91) in males) had strong associations with comorbidity at age 17 relative to having neither depression or overweight. Financial difficulties were also a risk factor in females, with less clear results in males. These findings highlight how early socioeconomic circumstances are linked with the accumulation of mental and physical health problems already in adolescence, which has implications for life-long health inequalities.

Establishing the relationships between adiposity and reproductive factors: a multivariable Mendelian randomization analysis.

BACKGROUND: Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's health. Here we assess whether adiposity at different points in the lifecourse affects reproductive factors differently and independently, and the plausibility of the impact of reproductive factors on adiposity. METHODS: We used genetic data from UK Biobank (273,238 women) and other consortia (EGG, GIANT, ReproGen and SSGAC) for eight reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners, and two adiposity traits: childhood and adulthood body size. We applied multivariable Mendelian randomization to account for genetic correlation and to estimate the causal effects of childhood and adulthood adiposity, independently of each other, on reproductive factors. Additionally, we estimated the effects of reproductive factors, independently of other relevant reproductive factors, on adulthood adiposity. RESULTS: We found a higher childhood body size leads to an earlier age at menarche, and an earlier age at menarche leads to a higher adulthood body size. Furthermore, we find contrasting and independent effects of childhood and adulthood body size on age at first birth (beta 0.22 SD (95% confidence interval: 0.14, 0.31) vs - 2.49 (- 2.93, - 2.06) per 1 SD increase), age at last birth (0.13 (0.06,0.21) vs - 1.86 (- 2.23, - 1.48) per 1 SD increase), age at menopause (0.17 (0.09, 0.25) vs - 0.99 (- 1.39, - 0.59) per 1 SD increase), and likelihood of having children (Odds ratio 0.97 (0.95, 1.00) vs 1.20 (1.06, 1.37) per 1 SD increase). CONCLUSIONS: Our findings demonstrate the importance of considering a lifecourse approach when investigating the inter-relationships between adiposity measures and reproductive events, as well as the use of 'age specific' genetic instruments when evaluating lifecourse hypotheses in a Mendelian randomization framework.

Is Height2.7 Appropriate for Indexation of Left Ventricular Mass in Healthy Adolescents? The Importance of Sex Differences.

BACKGROUND: Left ventricular mass (LVM) is an important predictor of cardiovascular risk. In adolescence, LVM is commonly indexed to height2.7, although some evidence suggests that this may not fully account for sex differences. METHODS: We investigated appropriate allometric scaling of LVM to height, total lean mass, and body surface area, in a UK birth cohort of 2039 healthy adolescents (17±1 years). Allometric relationships were determined by linear regression stratified by sex, following log transformation of x and y variables [log(y)=a+b×log(x)], b is the allometric exponent. RESULTS: Log (LVM) showed linear relationships with log(height) and log(lean mass). Biased estimates of slope resulted when the sexes were pooled. The exponents were lower than the conventional estimate of 2.7 for males (mean [95% CI]=1.66 [1.30-2.03]) and females (1.58 [1.27-1.90]). When LVM was indexed to lean mass, the exponent was 1.16 (1.05-1.26) for males and 1.07 (0.97-1.16) for females. When LVM was indexed to estimated body surface area, the exponent was 1.53 (1.40-1.66) for males and 1.34 (1.24-1.45) for females. CONCLUSIONS: Allometric exponents derived from pooled data, including men and women without adjustment for sex were biased, possibly due to sex differences in body composition. We suggest that when assessing LVM, clinicians should consider body size, body composition, sex, and age. Our observations may also have implications for the identification of young individuals with cardiac hypertrophy.

Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

BACKGROUND: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. METHODS: Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. RESULTS: The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. CONCLUSIONS: Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.

Using the Primary care Academic CollaboraTive to explore the characteristics and healthcare use of older housebound patients in England: protocol for a retrospective observational study and clinician survey (the CHiP study).

BACKGROUND: Older housebound people are an under-researched group for whom achieving good primary health care can be resource intensive. AIMS: To describe the characteristics and healthcare use of older (≥65 years) housebound people; explore clinician views on delivery of care to housebound people; and assess the feasibility of using a new network of healthcare professionals to deliver high quality research. DESIGN & SETTING: Retrospective observational study of electronic GP records and clinician survey in England. METHOD: Clinical members of a new UK research network called the Primary care Academic CollaboraTive (PACT) will collect the data. For part A, around 20 GP practices will be recruited and clinicians will identify 20 housebound and 20 non-housebound people, matched by age and gender (around 400 total in each group). Anonymised data will be collected on characteristics (age, gender, ethnicity, deprivation decile), long-term conditions, prescribed medicines, quality of healthcare (via Quality Outcomes Framework targets), and continuity of care. Reports with benchmarked practice-level data will be provided to practices to identify areas for quality improvement and to enhance engagement. For part B, 2-4 clinicians will be recruited from around 50 practices in England (around 150 clinicians) to complete a survey about delivery of healthcare for housebound people. For part C, data will be collected to assess the feasibility of using the PACT network to deliver primary care research. CONCLUSION: Older housebound people are a neglected group both in terms of research and clinical care. Understanding the characteristics and use of primary healthcare of housebound people will help identify how to improve their care.

Family adversity and health characteristics associated with intimate partner violence in children and parents presenting to health care: a population-based birth cohort study in England.

BACKGROUND: Little is known about the clinical characteristics of children and parents affected by intimate partner violence (IPV) presenting in health-care settings. We examined the associations between family adversities, health characteristics, and IPV in children and parents using linked electronic health records (EHRs) from primary and secondary care between 1 year before and 2 years after birth (the first 1000 days). We compared parental health problems in in children and parents with and without recorded IPV. METHODS: We developed a population-based birth cohort of children and parents (aged 14-60 years) in England, comprising linked EHRs from mother-child pairs (with no identified father) and mother-father-child triads. We followed the cohort across general practices (Clinical Practice Research Datalink GOLD), emergency departments, outpatient visits, hospital admissions, and mortality records. Family adversities included 33 clinical indicators of parental mental health problems, parental substance misuse, adverse family environments, and high-risk child maltreatment-related presentations. Parental health problems included 12 common comorbidities, ranging from diabetes and cardiovascular diseases to chronic pain or digestive diseases. We used adjusted and weighted logistic-regression models to estimate the probability of IPV (per 100 children and parents) associated with each adversity, and period prevalences of parental health problems associated with IPV. FINDINGS: We included 129 948 children and parents, comprising 95 290 (73·3%) mother-father-child triads and 34 658 (26·7%) mother-child pairs only between April 1, 2007, and Jan 29, 2020. An estimated 2689 (2·1%) of 129 948 children and parents (95% CI 2·0-2·3) had recorded IPV and 54 758 (41·2%; 41·5-42·2) had any family adversity between 1 year before and 2 years after birth. All family adversities were significantly associated with IPV. Most parents and children with IPV had recorded adversities (1612 [60·0%] of 2689) before their first IPV recording. The probability of IPV was 0·6 per 100 children and parents (95% CI 0·5-0·6) with no adversity, increasing to 4·4 per 100 children per parents (4·2-4·7) with one adversity, and up to 15·1 per 100 parents and children (13·6-16·5) with three of more adversities. Mothers with IPV had a significantly higher prevalence of both physical (73·4% vs 63·1%, odds ratio [OR] 1·6, 95% CI 1·4-1·8) and mental health problems (58·4% vs 22·2%, OR 4·9, 4·4-5·5) than mothers without IPV. Fathers with IPV had a higher prevalence of mental health problems (17·8% vs 7·1%, OR 2·8, 2·4-3·2) and similar prevalences of physical health problems than those without IPV (29·6% vs 32·4%, OR 0·9, 0·8-1·0). INTERPRETATION: Two in five of the children and parents presenting to health care had recorded parental mental health problems, parental substance misuse, adverse family environments, or high-risk presentations of maltreatment in the first 1000 days. One in 22 children and parents with family adversity also had recorded IPV before age 2 years. Primary and secondary care staff should safely ask about IPV when parents or children present with family adversity or health problems associated with IPV, and respond appropriately. FUNDING: NIHR Policy Research Programme.

Mediation and moderation of genetic risk of obesity through eating behaviours in two UK cohorts.

BACKGROUND: The mechanisms underlying genetic predisposition to higher body mass index (BMI) remain unclear. METHODS: We hypothesized that the relationship between BMI-genetic risk score (BMI-GRS) and BMI was mediated via disinhibition, emotional eating and hunger, and moderated by flexible (but not rigid) restraint within two UK cohorts: the Genetics of Appetite Study (GATE) (n = 2101, 2010-16) and the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 1679, 2014-18). Eating behaviour was measured by the Adult Eating Behaviour Questionnaire and Three-Factor Eating Questionaire-51. RESULTS: The association between BMI-GRS and BMI were partially mediated by habitual, emotional and situational disinhibition in the GATE/ALSPAC meta-mediation [standardized betaindirect 0.04, 95% confidence interval (CI) 0.02-0.06; 0.03, 0.01-0.04; 0.03, 0.01-0.04, respectively] external hunger and internal hunger in the GATE study (0.02, 0.01-0.03; 0.01, 0.001-0.02, respectively). There was evidence of mediation by emotional over/undereating and hunger in the ALSPAC study (0.02, 0.01-0.03; 0.01, 0.001-0.02; 0.01, 0.002-0.01, respectively). Rigid or flexible restraint did not moderate the direct association between BMI-GRS and BMI, but high flexible restraint moderated the effect of disinhibition subscales on BMI (reduction of the indirect mediation by -5% to -11% in GATE/ALSPAC) and external hunger (-5%) in GATE. High rigid restraint reduced the mediation via disinhibition subscales in GATE/ALSPAC (-4% to -11%) and external hunger (-3%) in GATE. CONCLUSIONS: Genetic predisposition to a higher BMI was partly explained by disinhibition and hunger in two large cohorts. Flexible/rigid restraint may play an important role in moderating the impact of predisposition to higher BMI.