Head motion in the UK Biobank imaging subsample: longitudinal stability, associations with psychological and physical health, and risk of incomplete data.

Participant motion in brain magnetic resonance imaging is associated with processing problems including potentially non-useable/incomplete data. This has implications for representativeness in research. Few large studies have investigated predictors of increased motion in the first instance. We exploratively tested for association between multiple psychological and physical health traits with concurrent motion during T1 structural, diffusion, average resting-state and task functional magnetic resonance imaging in N = 52 951 UK Biobank imaging subsample participants. These traits included history of cardiometabolic, inflammatory, neurological and psychiatric conditions, as well as concurrent cognitive test scores and anthropometric traits. We tested for stability in motion in participants with longitudinal imaging data (n = 5305, average 2.64 years later). All functional and T1 structural motion variables were significantly intercorrelated (Pearson r range 0.3-0.8, all P < 0.001). Diffusion motion variables showed weaker correlations around r = 0.1. Most physical and psychological phenotypes showed significant association with at least one measure of increased motion including specifically in participants with complete useable data (highest ß = 0.66 for diabetes versus resting-state functional magnetic resonance imaging motion). Poorer values in most health traits predicted lower odds of complete imaging data, with the largest association for history of traumatic brain injury (odds ratio = 0.720, 95% confidence interval = 0.562 to 0.923, P = 0.009). Worse psychological and physical health are consistent predictors of increased average functional and structural motion during brain imaging and associated with lower odds of complete data. Average motion levels were largely consistent across modalities and longitudinally in participants with repeat data. Together, these findings have implications for representativeness and bias in imaging studies of generally healthy population samples.

How do lifestyle factors modify the association between genetic predisposition and obesity-related phenotypes? A 4-way decomposition analysis using UK Biobank.

BACKGROUND: Obesity and central obesity are multifactorial conditions with genetic and non-genetic (lifestyle and environmental) contributions. There is incomplete understanding of whether lifestyle modifies the translation from respective genetic risks into phenotypic obesity and central obesity, and to what extent genetic predisposition to obesity and central obesity is mediated via lifestyle factors. METHODS: This is a cross-sectional study of 201,466 (out of approximately 502,000) European participants from UK Biobank and tested for interactions and mediation role of lifestyle factors (diet quality; physical activity levels; total energy intake; sleep duration, and smoking and alcohol intake) between genetic risk for obesity and central obesity. BMI-PRS and WHR-PRS are exposures and obesity and central obesity are outcomes. RESULTS: Overall, 42.8% of the association between genetic predisposition to obesity and phenotypic obesity was explained by lifestyle: 0.9% by mediation and 41.9% by effect modification. A significant difference between men and women was found in central obesity; the figures were 42.1% (association explained by lifestyle), 1.4% (by mediation), and 40.7% (by modification) in women and 69.6% (association explained by lifestyle), 3.0% (by mediation), and 66.6% (by modification) in men. CONCLUSIONS: A substantial proportion of the association between genetic predisposition to obesity/central obesity and phenotypic obesity/central obesity was explained by lifestyles. Future studies with repeated measures of obesity and lifestyle would be needed to clarify causation.

Educational outcomes among children with congenital heart disease compared to peers: a Scotland-wide record-linkage study of 715,850 schoolchildren.

BACKGROUND: Nine in every thousand children born in the United Kingdom have congenital heart disease, and 250,000 adults are living with the condition. This study aims to investigate the associations between congenital heart disease and educational outcomes among school-aged children in Scotland. METHODS: Routine health and education databases were linked to produce a cohort of all singleton children born in Scotland and attending a local authority run primary, secondary, or special school in Scotland at some point between 2009 and 2013. Children with congenital heart disease within this cohort were compared with children unaffected by congenital conditions. Outcomes investigated were special educational need (SEN), absenteeism, exclusion, academic attainment, and unemployment. All analyses were adjusted for sociodemographic and maternity confounders. Absenteeism was investigated as a mediating factor in the associations with attainment and unemployment. RESULTS: Of the 715,850 children, 6,295 (0.9%) had congenital heart disease and 4,412 (6.1%) had isolated congenital heart disease. Congenital heart disease and isolated congenital heart disease were both significantly associated with subsequent special educational need (OR 3.45, 95% CI 3.26-3.65, p < 0.001 and OR 1.98, 95% CI 1.84-2.13, p < 0.001 respectively), absenteeism (IRR 1.13, 95% CI 1.10-1.16, p < 0.001 and IRR 1.10, 95% CI 1.06-1.13, p < 0.001 respectively), and low academic attainment (OR 1.69, 95% CI 1.39-2.07, p < 0.001 and OR 1.35, 95% CI 1.07-1.69, p = 0.011 respectively). Neither congenital heart disease nor isolated congenital heart disease were associated with school exclusion. Only congenital heart disease (OR 1.21, 95% CI 1.03-1.42, p = 0.022) but not isolated congenital heart disease was associated with unemployment. When days absent were included in the analyses investigating attainment and unemployment, the conclusions were not altered. CONCLUSION: Children with congenital heart disease have greater special educational need, lower school attendance, attain lower examination grades and have greater unemployment compared to peers. In addition to healthcare support, affected children need educational support to avoid additional impact on their long-term wellbeing.

Methods applied to neonatal dried blood spot samples for secondary research purposes: a scoping review.

This scoping review aimed to synthesize the analytical techniques used and methodological limitations encountered when undertaking secondary research using residual neonatal dried blood spot (DBS) samples. Studies that used residual neonatal DBS samples for secondary research (i.e. research not related to newborn screening for inherited genetic and metabolic disorders) were identified from six electronic databases: Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, PubMed and Scopus. Inclusion was restricted to studies published from 1973 and written in or translated into English that reported the storage, extraction and testing of neonatal DBS samples. Sixty-seven studies were eligible for inclusion. Included studies were predominantly methodological in nature and measured various analytes, including nucleic acids, proteins, metabolites, environmental pollutants, markers of prenatal substance use and medications. Neonatal DBS samples were stored over a range of temperatures (ambient temperature, cold storage or frozen) and durations (two weeks to 40.5 years), both of which impacted the recovery of some analytes, particularly amino acids, antibodies and environmental pollutants. The size of DBS sample used and potential contamination were also cited as methodological limitations. Residual neonatal DBS samples retained by newborn screening programs are a promising resource for secondary research purposes, with many studies reporting the successful measurement of analytes even from neonatal DBS samples stored for long periods of time in suboptimal temperatures and conditions.

Schizophrenia and Types of Stroke: A Mendelian Randomization Study.

BACKGROUND: Previous studies suggest an association between schizophrenia and stroke, but no studies have investigated stroke subtypes. We examined potential causal associations between schizophrenia and a range of atherosclerotic, embolic, and hemorrhagic stroke outcomes. METHODS AND RESULTS: Two-sample Mendelian randomization analyses were conducted. The summary-level data (restricted to European ancestry) were obtained for schizophrenia and stroke: ischemic stroke, large-artery stroke, small-vessel stroke, cardioembolic stroke, and intracerebral hemorrhage. The associations between schizophrenia and each outcome were analyzed by an inverse variance weighting method primarily and Mendelian randomization Egger, weighted median, and weighted mode subsequently. The presence of pleiotropy was also tested by Cochran Q statistic, I2 index, and Mendelian randomization Egger intercept with scatter and funnel plots. We found associations between schizophrenia and cardioembolic stroke (odds ratio [OR], 1.070 [95% CI, 1.023-1.119]) and intracerebral hemorrhage (OR, 1.089 [95% CI, 1.005-1.180]) using inverse variance weighting. Little evidence of associations with the other stroke subtypes was found. Different Mendelian randomization methods corroborated the association with cardioembolic stroke but not intracerebral hemorrhage. CONCLUSIONS: We have provided evidence of a potentially causal association between schizophrenia and cardioembolic stroke. Our findings suggest that cardiac evaluation should be considered for those with schizophrenia.

Prospective study design and data analysis in UK Biobank.

Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.

In people with type 2 diabetes, sarcopenia is associated with the incidence of cardiovascular disease: A prospective cohort study from the UK Biobank.

AIM: To investigate the association of sarcopenia with cardiovascular disease (CVD) incidence in people with type 2 diabetes. MATERIALS AND METHODS: A prospective cohort study with 11 974 White European UK Biobank participants with type 2 diabetes, aged 40-70 years, included. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People as either non-sarcopenic or sarcopenic. Outcomes included CVD, stroke, heart failure (HF) and myocardial infarction (MI). The association between sarcopenia and the incidence of outcomes was investigated using Cox proportional hazard models adjusted for sociodemographic and lifestyle factors. The rate advancement period was used to estimate the time period by which CVD is advanced because of sarcopenia. RESULTS: Over a median follow-up of 10.7 years, 1957 participants developed CVDs: 373 had a stroke, 307 had an MI and 742 developed HF. Compared with non-sarcopenia, those with sarcopenia had higher risks of CVD (HR 1.89 [95% CI 1.61; 2.21]), HF (HR 2.59 [95% CI 2.12; 3.18]), stroke (HR 1.90 [95% CI 1.38; 2.63]), and MI (HR 1.56 [95% CI 1.04; 2.33]) after adjustment for all covariates. Those with sarcopenia had CVD incidence rates equivalent to those without sarcopenia who were 14.5 years older. Similar results were found for stroke, HF and MI. CONCLUSIONS: In people with type 2 diabetes, sarcopenia increased the risk of developing CVD, which might occur earlier than in those without sarcopenia. Therefore, sarcopenia screening and prevention in patients with type 2 diabetes may be useful to prevent the complications of CVD.

The impact of COVID-19 and associated lockdowns on traumatic spinal cord injury incidence: a population based study.

STUDY DESIGN: Natural experiment OBJECTIVES: To determine whether COVID-19 restrictions were associated with changes in the incidence of traumatic spinal cord injury (TSCI) in Scotland. SETTING: The Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole provider of treatment for TSCI in Scotland. METHODS: Time series analysis of all admissions for TSCI between 1st January 2015 and 31st August 2022. RESULTS: Over the 8-year study period, 745 patients were admitted to the QENSIU with a TSCI. Interrupted time series analysis showed that level 3 and 4 COVID-19 lockdown restrictions (the most severe levels) were associated with lower incidence of TSCI (RR 0.63, CI% CI 0.47, 0.82, p < 0.001). The associations were stronger in people aged over 45 (additive interaction p = 0.001), males (additive interaction p = 0.01) and non-tetraplegia (additive interaction p = 0.002). The incidence of TSCI due to deliberate self-harm was higher (0.41 versus 0.23 per month) during restrictions. CONCLUSIONS: Overall, TSCI incidence reduced in Scotland when lockdowns were implemented, presumably due to lower engagement in risky activities. The increase in TSCI due to deliberate self-harm may reflect increased mental health problems and social isolation and should be anticipated and targeted in future pandemics. The change in incidence during the COVID-19 pandemic may have an economic impact and see a temporary reduction in the burden on health and social care. The results of this study will be useful for resource planning in future pandemics.

Association of Stair Use With Risk of Major Chronic Diseases.

INTRODUCTION: Physical inactivity is associated with a higher risk of chronic diseases. Regular stair use can contribute to increasing physical activity in the population. This study aimed to investigate the association between flights of stairs used daily at home and all-cause mortality and cause-specific incidence and mortality. METHODS: Of the 502,628 UK Biobank participants recruited between 2007 and 2010, 442,027 (mean age, 56±8 years) had available data and were included in the analyses conducted in 2023. Participants were categorized on the basis of flights of stairs climbed daily (1-5, 6-10, 11-15, >15). The disease-specific outcomes were cardiovascular disease, respiratory disease, cancer, type 2 diabetes, and all-cause dementia. Cox proportional hazard models, adjusted for sociodemographic, lifestyle, and health-related confounding factors, were used to analyze the associations between stair use frequency and health outcomes. RESULTS: Participants were followed up for a median of 10.9 years. Climbing stairs >15 times per day was associated with a lower risk of 8 of the 9 outcomes analyzed than not using stairs. The magnitude of association ranged from 3% (95% CI=0.94, 0.99) lower risk for all-cause cancer to 51% (95% CI=0.39, 0.60) lower risk of chronic obstructive pulmonary disease. Findings were similar for mortality outcomes, with the hazard ratios ranging from 0.82 (95% CI=0.77, 0.87) for all-cause cancer to 0.46 (95% CI=0.23, 0.92) for chronic obstructive pulmonary disease mortality. CONCLUSIONS: Stair use was associated with a lower risk of all-cause mortality and cause-specific incidence and mortality independent of confounding factors, including adiposity and multimorbidity.

Association of five diet scores with severe NAFLD incidence: A prospective study from UK Biobank.

AIM: This study aimed to contrast the associations of five common diet scores with severe non-alcoholic fatty liver disease (NAFLD) incidence. MATERIALS AND METHODS: In total, 162 999 UK Biobank participants were included in this prospective population-based study. Five international diet scores were included: the 14-Item Mediterranean Diet Adherence Screener (MEDAS-14), the Recommended Food Score (RFS), the Healthy Diet Indicator (HDI), the Mediterranean Diet Score and the Mediterranean-DASH Intervention for Neurodegenerative Delay score. As each score has different measurements and scales, all scores were standardized and categorized into quartiles. Cox proportional hazard models adjusted for confounder factors investigated associations between the standardized quartiles and severe NAFLD incidence. RESULTS: Over a median follow-up of 10.2 years, 1370 participants were diagnosed with severe NAFLD. When the analyses were fully adjusted, participants in quartile 4 using the MEDAS-14 and RFS scores, as well as those in quartiles 2 and 3 using the HDI score, had a significantly lower risk of severe incident NAFLD compared with those in quartile 1. The lowest risk was observed in quartile 4 for the MEDAS-14 score [hazard ratio (HR): 0.76 (95% confidence interval (CI): 0.62-0.94)] and the RFS score [HR: 0.82 (95% CI: 0.69-0.96)] and as well as in quartile 2 in the HDI score [HR: 0.80 (95% CI: 0.70-0.91)]. CONCLUSION: MEDAS-14, RFS and HDI scores were the strongest diet score predictors of severe NAFLD. A healthy diet might protect against NAFLD development irrespective of the specific approach used to assess diet. However, following these score recommendations could represent optimal dietary approaches to mitigate NAFLD risk.

Different Sources of Fiber Intake and Risk of 17 Specific Cancers and All Cancers Combined: Prospective Study of 364,856 Participants in the UK Biobank.

Inverse associations between dietary fiber (DF) and colorectal cancer risk are well-established. However, evidence is limited in relation to other cancer sites. This study, of 364,856 participants from the UK Biobank, aimed to evaluate the associations between total and source-specific partial DF and risk of 17 specific cancers and all cancers combined. Partial DF was derived from baseline touchscreen questionnaire data on cereal, bread, fruit, and vegetable intake. The outcomes were incident cancer at 17 sites and all cancers combined. Cox proportional hazards models were applied. Over a median 8.8-year follow-up period, 30,725 people were diagnosed with cancer. After adjusting for sociodemographic and lifestyle factors, those in the highest quintile of partial DF compared with the lowest quintile (<9.6 vs ≥19.1 g/day) had 10% lower risk of cancer overall, with the greatest risk reductions observed for cervical (hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.14; 0.82), esophageal (HR = 0.66, 95% CI: 0.52; 0.84), lung (HR = 0.67, 95% CI: 0.59; 0.76), bladder (HR = 0.72, 95% CI: 0.56; 0.91), and kidney (HR = 0.75, 95% CI: 0.61; 0.92) cancers. Associations between DF and lung cancer were observed only in current and former smokers. Higher DF intake, in particular cereal fiber and fruit and vegetable fiber, was associated with a lower risk of overall and multiple site-specific cancers.

Association between menstrual cycle phase and metabolites in healthy, regularly menstruating women in UK Biobank, and effect modification by inflammatory markers and risk factors for metabolic disease.

BACKGROUND: Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations. METHODS: We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables. RESULTS: Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively. CONCLUSIONS: Cholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women.

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

Life expectancy can increase by up to 10 years following sustained shifts towards healthier diets in the United Kingdom.

Adherence to healthy dietary patterns can prevent the development of non-communicable diseases and affect life expectancy. Here, using a prospective population-based cohort data from the UK Biobank, we show that sustained dietary change from unhealthy dietary patterns to the Eatwell Guide dietary recommendations is associated with 8.9 and 8.6 years gain in life expectancy for 40-year-old males and females, respectively. In the same population, sustained dietary change from unhealthy to longevity-associated dietary patterns is associated with 10.8 and 10.4 years gain in life expectancy in males and females, respectively. The largest gains are obtained from consuming more whole grains, nuts and fruits and less sugar-sweetened beverages and processed meats. Understanding the contribution of sustained dietary changes to life expectancy can provide guidance for the development of health policies.

True prevalence of long-COVID in a nationwide, population cohort study.

Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.

Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings. METHODS: Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders. RESULTS: Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range. CONCLUSIONS: In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.

Validating the SMART2 Score in a Racially Diverse High-Risk Nationwide Cohort of Patients Receiving Coronary Artery Bypass Grafting.

Background We tested the potential of the Secondary Manifestations of Arterial Disease (SMART2) risk score for use in patients undergoing coronary artery bypass grafting. Methods and Results We conducted an external validation of the SMART2 score in a racially diverse high-risk national cohort (2010-2019) that underwent isolated coronary artery bypass grafting. We calculated the preoperative SMART2 score and modeled the 5-year major adverse cardiovascular event (cardiovascular mortality+myocardial infarction+stroke) incidence. We evaluated SMART2 score discrimination at 5 years using c-statistic and calibration with observed/expected ratio and calibration plots. We analyzed the potential clinical benefit using decision curves. We repeated these analyses in clinical subgroups, diabetes, chronic kidney disease, and polyvascular disease, and separately in White and Black patients. In 27 443 (mean age, 65 years; 10% Black individuals) US veterans undergoing coronary artery bypass grafting (2010-2019) nationwide, the 5-year major adverse cardiovascular event rate was 25%; 27% patients were in high predicted risk (>30% 5-year major adverse cardiovascular events). SMART2 score discrimination (c-statistic: 64) was comparable to the original study (c-statistic: 67) and was best in patients with chronic kidney disease (c-statistic: 66). However, it underpredicted major adverse cardiovascular event rates in the whole cohort (observed/expected ratio, 1.45) as well as in all studied subgroups. The SMART2 score performed better in White than Black patients. On decision curve analysis, the SMART2 score provides a net benefit over a wide range of risk thresholds. Conclusions The SMART2 model performs well in a racially diverse coronary artery bypass grafting cohort, with better predictive capabilities at the upper range of baseline risk, and can therefore be used to guide secondary preventive pharmacotherapy.

Understanding covid-19 outcomes among people with intellectual disabilities in England.

BACKGROUND: Evidence from the UK from the early stages of the covid-19 pandemic showed that people with Intellectual Disabilities (ID) had higher rates of covid-19 mortality than people without ID. However, estimates of the magnitude of risk vary widely; different studies used different time periods; and only early stages of the pandemic have been analysed. Existing analyses of risk factors have also been limited. The objective of this study was to investigate covid-19 mortality rates, hospitalisation rates, and risk factors in people with ID in England up to the end of 2021. METHODS: Retrospective cohort study of all people with a laboratory-confirmed SARS-CoV-2 infection or death involving covid-19. Datasets covering primary care, secondary care, covid-19 tests and vaccinations, prescriptions, and deaths were linked at individual level. RESULTS: Covid-19 carries a disproportionately higher risk of death for people with ID, above their already higher risk of dying from other causes, in comparison to those without ID. Around 2,000 people with ID had a death involving covid-19 in England up to the end of 2021; approximately 1 in 180. The covid-19 standardized mortality ratio was 5.6 [95% CI 5.4, 5.9]. People with ID were also more likely to be hospitalised for covid-19 than people without ID. The main determinants of severe covid-19 outcomes (deaths and/or hospitalisations) in both populations were age, multimorbidity and vaccination status. The key factor responsible for the higher risk of severe covid-19 in the ID population was a much higher prevalence of multimorbidity in this population. AstraZeneca vaccine was slightly less effective in preventing severe covid-19 outcomes among people with ID than among people without ID. CONCLUSIONS: People with ID should be considered a priority group in future pandemics, such as shielding and vaccinations.

Corrigendum: A comparison of physical activity, muscle strength, and sleep between people with type 2 diabetes in Kuwait and he UK: a cross sectional study.

[This corrects the article DOI: 10.3389/fendo.2022.1067227.].

Consistent effects of the genetics of happiness across the lifespan and ancestries in multiple cohorts.

Happiness is a fundamental human affective trait, but its biological basis is not well understood. Using a novel approach, we construct LDpred-inf polygenic scores of a general happiness measure in 2 cohorts: the Adolescent Brain Cognitive Development (ABCD) cohort (N = 15,924, age range 9.23-11.8 years), the Add Health cohort (N = 9129, age range 24.5-34.7) to determine associations with several well-being and happiness measures. Additionally, we investigated associations between genetic scores for happiness and brain structure in ABCD (N = 9626, age range (8.9-11) and UK Biobank (N = 16,957, age range 45-83). We detected significant (p.FDR < 0.05) associations between higher genetic scores vs. several well-being measures (best r2 = 0.019) in children of multiple ancestries in ABCD and small yet significant correlations with a happiness measure in European participants in Add Health (r2 = 0.004). Additionally, we show significant associations between lower genetic scores for happiness with smaller structural brain phenotypes in a white British subsample of UK Biobank and a white sub-sample group of ABCD. We demonstrate that the genetic basis for general happiness level appears to have a consistent effect on happiness and wellbeing measures throughout the lifespan, across multiple ancestral backgrounds, and multiple brain structures.