Lifecourse Epidemiology

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BACKGROUND: Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B cell and immunoglobulin (Ig) production, and poor outcomes in ovarian cancer patients. No study has evaluated the impact of smoke exposure across the lifecourse on B cell infiltration and Ig abundance in ovarian tumors. METHODS: We measured markers of B and plasma cells and Ig isotypes using multiplex immunofluorescence on 395 ovarian cancer tumors in the Nurses' Health Study (NHS)/NHSII...

BACKGROUND: Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging. METHODS AND RESULTS: In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization...

BACKGROUND: Violence is a leading cause of death and disability for young people and has serious impacts on prospects across the lifecourse. The education sector is a crucial setting for preventing youth violence through incorporating programmes that address attitudes and behaviours. The Mentors in Violence Prevention (MVP) programme aims to change harmful attitudes and norms, and increase non-violent bystander intervention, through a peer mentoring approach. To date there is limited evidence on the effectiveness of the intervention in UK school settings...

Higher adult child educational attainment may benefit older parents' psychosocial well-being in later life. This may be particularly important in low- and middle-income countries, where recent generations have experienced comparatively large increases in educational attainment. We used data from the 2012 Mexican Health and Aging Study, a nationally representative study of adults aged ≥50 years and leveraged the exogenous variation in adult child education induced by Mexico's compulsory schooling law passed in 1993...

BACKGROUND: Emerging observational studies showed an association between atopic dermatitis (AD) and gastrointestinal cancers. However, it remains unclear whether this association is causal, particularly in the case of cancers like esophageal cancer, which exhibit ancestral genetic traits. METHODS: To assess the potential causal relationship between AD and esophageal cancer across diverse ancestral backgrounds, we conducted a 2-sample Mendelian randomization study...

Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n = 13,962 cases) and adult-onset asthma (n = 26,582 cases) with a common set of controls (n = 300,671) using a technique known as lifecourse Mendelian randomization...

OBJECTIVE: To investigate the accumulation of adversities (duration of exposure to any, economic, psychosocial) across the lifecourse (birth to 63 years) on cognitive function in older age, and the mediating role of mental health. DESIGN: National birth cohort study. SETTING: Great Britain. PARTICIPANTS: 5362 singleton births within marriage in England, Wales and Scotland born within 1 week of March 1946, of which 2131 completed at least 1 cognitive assessment...

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...

Accumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers...

BACKGROUND: Associations between a high body mass index (BMI) at single timepoints during child- and adulthood and risks of post-menopausal breast cancer are well-established, but associations with BMI across the lifecourse remains largely unknown. Therefore, we examined whether lifecourse BMI trajectories were associated with risks of post-menopausal breast cancer overall and by estrogen receptor (ER) status. METHODS: We included 6698 Danish women born 1930-1946...

BACKGROUND: Findings from Mendelian randomization (MR) studies are conventionally interpreted as lifelong effects, which typically do not provide insight into the molecular mechanisms underlying the effect of an exposure on an outcome. In this study, we apply two recently developed MR approaches (known as 'lifecourse' and 'tissue-partitioned' MR) to investigate lifestage-specific effects and tissues of action in the relationship between adiposity and circulating leptin levels. METHODS: Genetic instruments for childhood and adult adiposity were incorporated into a multivariable MR (MVMR) framework to estimate lifestage-specific effects on leptin levels measured during early life (mean age: 10 y) in the Avon Longitudinal Study of Parents and Children and in adulthood (mean age: 55 y) using summary-level data from the deCODE Health study...

INTRODUCTION: Sarcopenic obesity (SarcO) is defined as the confluence of reduced muscle mass and function and excess body fat. The scientific community is increasingly recognizing this syndrome, which affects a subgroup of persons across their lifespans and places them at synergistically higher risk of significant medical comorbidity and disability than either sarcopenia or obesity alone. Joint efforts in clinical and research settings are imperative to better understand this syndrome and drive the development of urgently needed future interventions...

Black women in the U.S. have the highest incidence of hypertensive disorders of pregnancy (HDP) and are disproportionately burdened by its adverse sequalae compared to women of all racial and ethnic groups. Segregation, a key driver of structural racism for Black families, can provide critical information to understanding these disparities. We examined the association between racial and economic segregation at two points and incident HDP using intergenerationally linked birth records of 45,204 Black California-born primiparous mothers (born 1982-1997) and their infants (born 1997-2011), with HDP ascertained from hospital discharge records...

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Comparing outcomes for individuals remaining married to those for single or divorced individuals might overstate the positive effects of the decision to marry, since marriage carries an inherent risk of divorce and its associated negative outcomes. While a growing literature has examined marital transitions, confounding by past marital history remains a concern and only a limited set of outcomes have been examined. To address these issues, this study examined incident first-time marriage and incident divorce/separation in relation to multiple subsequent physical health, health behavior, psychological distress, and psychosocial well-being outcomes in a large sample of female nurses in the U...

BACKGROUND: Migraine is a very common headache disorder on the population level, characterized by symptomatic attacks (activity). For many people with migraine, the migraine symptoms intermittently or permanently cease during their lifetime (inactive migraine). The current diagnostic classification of migraine considers two states: active migraine (having migraine symptoms within the last year) and not having active migraine (including both individuals with inactive migraine and those who never had migraine)...

Incomplete longitudinal data are common in life-course epidemiology and may induce bias leading to incorrect inference. Multiple imputation (MI) is increasingly preferred for handling missing data, but few studies explore MI-method performance and feasibility in real-data settings. We compared 3 MI methods using real data under 9 missing-data scenarios, representing combinations of 10%, 20%, and 30% missingness and missing completely at random, at random, and not at random. Using data from Health and Retirement Study (HRS) participants, we introduced record-level missingness to a sample of participants with complete data on depressive symptoms (1998-2008), mortality (2008-2018), and relevant covariates...

Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a huge disease burden. Attention-deficit/hyperactivity disorder (ADHD) is often diagnosed in children, and is associated with symptoms of inattention, hyperactivity and impulsive behaviour. Observational studies have demonstrated associations between AD and ADHD. However, to date, there has been no formal assessment of causal relationship between the two. We aim to evaluate causal relationships between genetically increased risk of AD and ADHD using Mendelian randomization (MR) approach...

At times of major geopolitical conflict, macroeconomic crisis and the 'aftershocks' of the COVID-19 syndemic still having a global impact, it is the most vulnerable and disadvantaged in society who undoubtedly suffer the most. During these turbulent and uncertain times, it is essential that sufficient policy attention is given to tackling the persistent and stark health inequalities that exist both between and within countries. This commentary aims to critically reflect on developments in oral health inequalities research, policy and practice over the last 50 years...