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.

A phenome-wide approach to identify causal risk factors for deep vein thrombosis.

Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein. DVT can lead to a venous thromboembolism (VTE), the combined term for DVT and pulmonary embolism, a leading cause of death and disability worldwide. Despite the prevalence and associated morbidity of DVT, the underlying causes are not well understood.

Body mass index in parents and their adult offspring: A systematic review and meta-analysis.

Obesity may track across generations, due to genetics and shared family environmental factors, or possibly intrauterine programming. However, many studies only assess associations between maternal body mass index (BMI) and offspring BMI in childhood. To determine whether maternal and paternal associations with offspring BMI differ and whether associations persist into adulthood, a systematic review and meta-analysis was done.

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.

Placental syndromes and maternal cardiovascular health.

The placental syndromes gestational hypertension, preeclampsia and intrauterine growth restriction are associated with an increased cardiovascular risk to the mother later in life. In this review, we argue that a woman's pre-conception cardiovascular health drives both the development of placental syndromes and long-term cardiovascular risk but acknowledge that placental syndromes can also contribute to future cardiovascular risk independent of pre-conception health. We describe how preclinical studies in models of preeclampsia inform our understanding of the links with later cardiovascular disease, and how current pre-pregnancy studies may explain relative contributions of both pre-conception factors and the occurrence of placental syndromes to long-term cardiovascular disease.

An observational analysis of risk factors associated with symptomatic third molar teeth.

Background: Third molar teeth (wisdom teeth) are a common cause of pain and infection in young adults. The study aimed to describe the prevalence of symptomatic third molar teeth and identify factors which predispose to third molar symptoms in a birth cohort.

Methods: An observational study was undertaken nested in the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort based in south west England.

Multivariate genome-wide analysis of aging-related traits identifies novel loci and new drug targets for healthy aging.

The concept of aging is complex, including many related phenotypes such as healthspan, lifespan, extreme longevity, frailty and epigenetic aging, suggesting shared biological underpinnings; however, aging-related endpoints have been primarily assessed individually. Using data from these traits and multivariate genome-wide association study methods, we modeled their underlying genetic factor ('mvAge'). mvAge (effective n = ~1.

Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction.

Objective: To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking.

Result: A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model.

Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ~800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ~11 and ~14-fold higher risk of delayed and precocious pubertal development, respectively.

Keeping up with the kids: the value of co-production in the study of irritability in youth depression and its underlying neural circuitry.

Irritability is a core symptom of adolescent depression, characterized by an increased proneness to anger or frustration. Irritability in youth is associated with future mental health problems and impaired social functioning, suggesting that it may be an early indicator of emotion regulation difficulties. Adolescence is a period during which behavior is significantly impacted by one's environment.

Glycoprotein acetyls and depression: Testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses.

Background: Inflammation is associated with depression, but causality remains unclear. We investigated potential causality and direction of effect between inflammation and depression.

Methods: Using data from the ALSPAC birth cohort (n = 4021; 42.

Height, social position and coronary heart disease incidence: the contribution of genetic and environmental factors.

Background: The associations between height, socioeconomic position (SEP) and coronary heart disease (CHD) incidence are well established, but the contribution of genetic factors to these associations is still poorly understood. We used a polygenic score (PGS) for height to shed light on these associations.

Methods: Finnish population-based health surveys in 1992-2011 (response rates 65-93%) were linked to population registers providing information on SEP and CHD incidence up to 2019.

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.

Chromosome 18 Loss of Heterozygosity in Small Intestinal Neuroendocrine Tumours: Multi-Omic and Tumour Composition Analyses.

Introduction: Small intestinal neuroendocrine tumours (siNETs) are rare neoplasms which present with low mutational burden and can be subtyped based on copy number variation (CNV). Currently, siNETs can be molecularly classified as having chromosome 18 loss of heterozygosity (18LOH), multiple CNVs (MultiCNV), or no CNVs. 18LOH tumours have better progression-free survival when compared to MultiCNV and NoCNV tumours, however, the mechanism underlying this is unknown, and clinical practice does not currently consider CNV status.