Adiposity and mortality among intensive care patients with COVID-19 and non-COVID-19 respiratory conditions: a cross-context comparison study in the UK.

Background: Adiposity shows opposing associations with mortality within COVID-19 versus non-COVID-19 respiratory conditions. We assessed the likely causality of adiposity for mortality among intensive care patients with COVID-19 versus non-COVID-19 by examining the consistency of associations across temporal and geographical contexts where biases vary.

Methods: We used data from 297 intensive care units (ICUs) in England, Wales, and Northern Ireland (Intensive Care National Audit and Research Centre Case Mix Programme).

Evaluation and comparison of nine growth and development-based measures of pubertal timing.

Background: Pubertal timing is heritable, varies between individuals, and has implications for life-course health. There are many different indicators of pubertal timing, and how they relate to each other is unclear. Our aim was to quantitatively compare nine indicators of pubertal timing.

Life course plasma metabolomic signatures of genetic liability to Alzheimer's disease.

Mechanisms through which most known Alzheimer's disease (AD) loci operate to increase AD risk remain unclear. Although Apolipoprotein E (APOE) is known to regulate lipid homeostasis, the effects of broader AD genetic liability on non-lipid metabolites remain unknown, and the earliest ages at which metabolic perturbations occur and how these change over time are yet to be elucidated. We examined the effects of AD genetic liability on the plasma metabolome across the life course.

Identifying metabolic features of colorectal cancer liability using Mendelian randomization.

Background: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival.

Methods: To investigate whether changes in circulating metabolites characterize the early stages of colorectal cancer (CRC) development, we examined the associations between a genetic risk score (GRS) associated with CRC liability (72 single-nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N = 6221). Linear regression models were applied to examine the associations between genetic liability to CRC and circulating metabolites measured in the same individuals at age 8 y, 16 y, 18 y, and 25 y.

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.

Life course effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study.

Background/objectives: Different genetic variants are associated with larger body size in childhood vs adulthood. Whether and when these variants predominantly influence adiposity are unknown. We examined how genetic variants influence total body fat and total lean mass trajectories.

Identifying metabolic features of colorectal cancer liability using Mendelian randomization.

Background: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival.

Methods: To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years.

Sex-specific trajectories of molecular cardiometabolic traits from childhood to young adulthood.

Background: The changes which typically occur in molecular causal risk factors and predictive biomarkers for cardiometabolic diseases across early life are not well characterised.

Methods: We quantified sex-specific trajectories of 148 metabolic trait concentrations including various lipoprotein subclasses from age 7 years to 25 years. Data were from 7065 to 7626 offspring (11 702 to14 797 repeated measures) of the Avon Longitudinal Study of Parents and Children birth cohort study.

Distinct metabolic features of genetic liability to type 2 diabetes and coronary artery disease: a reverse Mendelian randomization study.

Background: Type 2 diabetes (T2D) and coronary artery disease (CAD) both have known genetic determinants, but the mechanisms through which their associated genetic variants lead to disease onset remain poorly understood.

Methods: We used large-scale metabolomics data in a two-sample reverse Mendelian randomization (MR) framework to estimate effects of genetic liability to T2D and CAD on 249 circulating metabolites in the UK Biobank (N = 118,466). We examined the potential for medication use to distort effect estimates by conducting age-stratified metabolite analyses.

Strategies to investigate and mitigate collider bias in genetic and Mendelian randomisation studies of disease progression.

Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors that influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as "index event") bias since the disease progression phenotype can only be observed for individuals who have the disease.

Attitudes and uses of archival materials among science-based anthropologists.

While archival user studies have largely focused on humanities (and adjacent) scholars, this paper focuses on anthropologists engaged in scientific research. Based on qualitative results from an open-ended survey, we investigate how science-based anthropologists perceive and use archives in their work. We ask: How are science-based anthropologists and archaeologists reusing archival data in their research? What difficulties or barriers do they encounter in reusing archival data in scientific contexts? What attitudes or understandings about archival research are held by science-based anthropologists and archaeologists? Our findings primarily add to the body of literature about user experience in archives and more broadly to the emerging literature on archival data reuse.

Effects of general and central adiposity on circulating lipoprotein, lipid, and metabolite levels in UK Biobank: A multivariable Mendelian randomization study.

Background: The direct effects of general adiposity (body mass index (BMI)) and central adiposity (waist-to-hip-ratio (WHR)) on circulating lipoproteins, lipids, and metabolites are unknown.

Methods: We used new metabolic data from UK Biobank (=109,532, a five-fold higher N over previous studies). EDTA-plasma was used to quantify 249 traits with nuclear-magnetic-resonance spectroscopy including subclass-specific lipoprotein concentrations and lipid content, plus pre-glycemic and inflammatory metabolites.

Should an Age Cutoff Be Considered for Elective Total Knee Arthroplasty Patients? An Analysis of Operative Success Based on Patient-Reported Outcomes.

Total knee arthroplasty (TKA) is increasing in the elderly population; however, some patients, family members, and surgeons raise age-related concerns over expected improvement and risks. This study aimed to (1) evaluate the relationship between age and change in patient-reported outcome measures (PROMs); (2) model how many patients would be denied improvements in PROMs if hypothetical age cutoffs were implemented; and (3) assess length of stay (LOS), readmission, reoperation, and mortality per age group. A prospective cohort of 4,396 primary TKAs (August 2015-August 2018) was analyzed.

Puberty Timing and Sex-Specific Trajectories of Systolic Blood Pressure: a Prospective Cohort Study.

Background: Sex differences in systolic blood pressure (SBP) emerge during adolescence but the role of puberty is not well understood. We examined sex-specific changes in SBP preceding and following puberty and examined the impact of puberty timing on SBP trajectories in females and males.

Methods: Trajectories of SBP before and after puberty and by timing of puberty in females and males in a contemporary birth cohort study were analyzed.

Applying Mendelian randomization to appraise causality in relationships between nutrition and cancer.

Dietary factors are assumed to play an important role in cancer risk, apparent in consensus recommendations for cancer prevention that promote nutritional changes. However, the evidence in this field has been generated predominantly through observational studies, which may result in biased effect estimates because of confounding, exposure misclassification, and reverse causality. With major geographical differences and rapid changes in cancer incidence over time, it is crucial to establish which of the observational associations reflect causality and to identify novel risk factors as these may be modified to prevent the onset of cancer and reduce its progression.

Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation.

Large-scale molecular profiling and genotyping provide a unique opportunity to systematically compare the genetically predicted effects of therapeutic targets on the human metabolome. We firstly constructed genetic risk scores for 8 drug targets on the basis that they primarily modify low-density lipoprotein (LDL) cholesterol (HMGCR, PCKS9, and NPC1L1), high-density lipoprotein (HDL) cholesterol (CETP), or triglycerides (APOC3, ANGPTL3, ANGPTL4, and LPL). Conducting mendelian randomisation (MR) provided strong evidence of an effect of drug-based genetic scores on coronary artery disease (CAD) risk with the exception of ANGPTL3.

Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation.

Background: Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases.

Body muscle gain and markers of cardiovascular disease susceptibility in young adulthood: A cohort study.

Background: The potential benefits of gaining body muscle for cardiovascular disease (CVD) susceptibility, and how these compare with the potential harms of gaining body fat, are unknown. We compared associations of early life changes in body lean mass and handgrip strength versus body fat mass with atherogenic traits measured in young adulthood.

Methods And Findings: Data were from 3,227 offspring of the Avon Longitudinal Study of Parents and Children (39% male; recruited in 1991-1992).

Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates.

Background: Variation in adiposity is associated with cardiometabolic disease outcomes, but mechanisms leading from this exposure to disease are unclear. This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins.

Methods: We used SomaLogic proteomic data from up to 2737 healthy participants from the INTERVAL study.

Evaluating the direct effects of childhood adiposity on adult systemic metabolism: a multivariable Mendelian randomization analysis.

Background: Individuals who are obese in childhood have an elevated risk of disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independently of adult adiposity, is unclear. In this study, we have simultaneously evaluated the effects of childhood and adulthood body size on 123 systemic molecular biomarkers representing multiple metabolic pathways.