Multiomic profiling reveals timing of menopause predicts prefrontal cortex aging and cognitive function.

A new case of dementia is diagnosed every 3 s. Beyond age, risk prediction of dementia is challenging. There is growing evidence of underlying processes that connect aging across organ systems and may provide insight for early detection, and there is a need to identify early biomarkers at an age when action can be taken to mitigate cognitive decline.

Mendelian randomization reveals apolipoprotein B shortens healthspan and possibly increases risk for Alzheimer's disease.

Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein cholesterol (LDL) and has been implicated in conditions that end healthspan (the interval between birth and onset of chronic disease). However, APOB's direct relationship with healthspan remains uncertain.

Trauma and female reproductive health across the lifecourse: motivating a research agenda for the future of women's health.

The aetiology behind many female reproductive disorders is poorly studied and incompletely understood despite the prevalence of such conditions and substantial burden they impose on women's lives. In light of evidence demonstrating a higher incidence of trauma exposure in women with many such disorders, we present a set of interlinked working hypotheses proposing relationships between traumatic events and reproductive and mental health that can define a research agenda to better understand reproductive outcomes from a trauma-informed perspective across the lifecourse. Additionally, we note the potential for racism to act as a traumatic experience, highlight the importance of considering the interaction between mental and reproductive health concerns, and propose several neuroendocrinological mechanisms by which traumatic experiences might increase the risk of adverse health outcomes in these domains.

Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics.

Unlabelled: Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available to guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA sequencing on 146 tumors and WES of matched germline DNA from 140 H/L women in California.

Lifestyle interventions to reduce endocrine-disrupting phthalate and phenol exposures among reproductive age men and women: A review and future steps.

Non-persistent endocrine-disrupting chemicals (EDCs), including phthalates and phenols, are ubiquitous in both the environment and human body. A growing body of epidemiologic studies have identified concerning links between EDCs and adverse reproductive and developmental health effects. Despite consistent evidence, risk assessments and policy interventions often arrive late.

Shared genomic architectures of COVID-19 and antisocial behavior.

Little is known about the genetics of norm violation and aggression in relation to coronavirus disease 2019 (COVID-19). To investigate this, we used summary statistics from genome-wide association studies and linkage disequilibrium score regression to calculate a matrix of genetic correlations (r) for antisocial behavior (ASB), COVID-19, and various health and behavioral traits. After false-discovery rate correction, ASB was genetically correlated with COVID-19 (r = 0.

Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout.

Observational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations (r). For data, we used genome-wide association study summary statistics available through MR-Base.

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood.

Can increasing years of schooling reduce type 2 diabetes (T2D)?: Evidence from a Mendelian randomization of T2D and 10 of its risk factors.

A focus in recent decades has involved examining the potential causal impact of educational attainment (schooling years) on a variety of disease and life-expectancy outcomes. Numerous studies have broadly revealed a link suggesting that as years of formal schooling increase so too does health and wellbeing; however, it is unclear whether the associations are causal. Here we use Mendelian randomization, an instrumental variables technique, with a two-sample design, to probe whether more years of schooling are causally linked to type 2 diabetes (T2D) and 10 of its attendant risk factors.

A Mendelian randomization study of telomere length and blood-cell traits.

Whether telomere attrition reducing proliferative reserve in blood-cell progenitors is causal has important public-health implications. Mendelian randomization (MR) is an analytic technique using germline genetic variants as instrumental variables. If certain assumptions are met, estimates from MR should be free from most environmental sources of confounding and reverse causation.

A multivariable Mendelian randomization to appraise the pleiotropy between intelligence, education, and bipolar disorder in relation to schizophrenia.

Education and intelligence are highly correlated and inversely associated with schizophrenia. Counterintuitively, education genetically associates with an increased risk for the disease. To investigate why, this study applies a multivariable Mendelian randomization of intelligence and education.

Circulating Glutamine and Alzheimer's Disease: A Mendelian Randomization Study.

Background: Alzheimer's disease is a devastating neurodegenerative disorder. Its worldwide prevalence is over 24 million and is expected to double by 2040. Finding ways to prevent its cognitive decline is urgent.

Bi-directional Mendelian randomization of epithelial ovarian cancer and schizophrenia and uni-directional Mendelian randomization of schizophrenia on circulating 1- or 2-glycerophosphocholine metabolites.

Most women with epithelial ovarian cancer (EOC) present with late-stage disease. As a result, globally, EOC is responsible for >150,000 deaths a year. Thus, a better understanding of risk factors for developing EOC is crucial for earlier screening and detection to improve survival.

Evaluating causal associations between chronotype and fatty acids and between fatty acids and type 2 diabetes: A Mendelian randomization study.

Background And Aims: Preference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and one potential T2D risk factor, total fatty acids (TOTFA), and between TOTFA and T2D.

Methods And Results: We estimated the causal effect of: 1) morning chronotype on TOTFA; and 2) higher TOTFA on T2D.

The Precautionary Principle for Shift-Work Research and Decision-Making.

Shift work (working outside of 6:00 AM to 6:00 PM) is a fixture of our 24-hour economy, with approximately 18 per cent of workers in the USA engaging in shift work, many overnight. Since shift work has been linked to an increased risk for an array of serious maladies, including cardiometabolic disorders and cancer, and is done disproportionately by the poor and by minorities, shift work is a highly prevalent economic and occupational health disparity. Here we draw primarily on the state of science around shift work and breast cancer to argue that shift work represents a public health threat serious enough to warrant a precautionary stance.

Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study.

Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

Methods: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial.

Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial.

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls.

A brief tour of epidemiologic epigenetics and mental health.

The epidemiologic study of DNA methylation (DNAm) and mental health is a burgeoning area, but confounding and reverse causation remain important to know about. Whether use of non-brain tissues is appropriate when investigating brain phenotypes depends on the hypothesis and whether the goal is causality or to identify biomarkers. Look-ups of the correspondence between DNAm in blood and brain and use of Mendelian randomization (MR) can be done to follow-up, to some degree, on the causal nature of some findings.

Nightshift work, chronotype, and genome-wide DNA methylation in blood.

Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.

Otologic manifestations of Fanconi anemia and other inherited bone marrow failure syndromes.

Background: The inherited bone marrow failure syndromes (IBMFSs) are diverse disorders with syndrome-specific features; their otologic and audiologic manifestations have not been well described. Our objective was to characterize these in patients with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS), and to determine the association between physical findings and hearing loss.

Methods: Patients with an IBMFS underwent comprehensive clinical and laboratory evaluations and testing for syndrome-specific gene mutations.

Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort.

Background: Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype.