No Evidence of Interaction Between FADS2 Genotype and Breastfeeding on Cognitive or Other Traits in the UK Biobank.

Breastfeeding is hypothesised to benefit child health and cognitive functioning by providing long-chain polyunsaturated fatty acids, which are essential for brain development. In 2007, Caspi et al. found evidence in two cohorts for an interaction between genetic variation in the FADS2 gene (a gene involved in fatty acid metabolism) and breastfeeding on IQ.

Accounting for bias due to outcome data missing not at random: comparison and illustration of two approaches to probabilistic bias analysis: a simulation study.

Background: Bias from data missing not at random (MNAR) is a persistent concern in health-related research. A bias analysis quantitatively assesses how conclusions change under different assumptions about missingness using bias parameters that govern the magnitude and direction of the bias. Probabilistic bias analysis specifies a prior distribution for these parameters, explicitly incorporating available information and uncertainty about their true values.

Multiomic Mendelian Randomization Study Investigating the Impact of PCSK9 and HMGCR Inhibition on Type 2 Diabetes Across Five Populations.

The prevalence of type 2 diabetes (T2D) varies among populations of different races/ethnicities. The influence of genetically proxied LDL cholesterol lowering through proprotein convertase subtilisin/kexin 9 (PCSK9) and HMG-CoA reductase (HMGCR) on T2D in non-European populations is not well established. A drug target Mendelian randomization approach was used to assess the effects of PCSK9 and HMGCR inhibition on T2D risk and glycemic traits in five populations: East Asian (EAS), South Asian (SAS), Hispanic (HISP), African (AFR), and Europe (EUR).

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).

Reclaiming mendelian randomization from the deluge of papers and misleading findings.

Mendelian randomization (MR) is a powerful epidemiological method for causal inference. However, its recent surge in popularity has brought two concerning trends. First, the public availability of summary results from genome-wide association studies has led to an explosion of low-quality two-sample mendelian randomization (2SMR) studies.

Role of Inflammation in Depressive and Anxiety Disorders, Affect, and Cognition: Genetic and Non-Genetic Findings in the Lifelines Cohort Study.

Inflammation is associated with a range of neuropsychiatric symptoms; however, the nature of the causal relationship is unclear. We used complementary non-genetic, genetic risk score (GRS), and Mendelian randomization (MR) analyses to examine whether inflammatory markers are associated with affect, depressive and anxiety disorders, and cognition. We tested in ≈ 55,098 (59% female) individuals from the Dutch Lifelines cohort the concurrent/prospective associations of C-reactive protein (CRP) with: depressive and anxiety disorders; positive/negative affect; and attention, psychomotor speed, episodic memory, and executive functioning.

Educational attainment and mental health conditions: a within-sibship Mendelian randomization study.

Importance: Observational studies have demonstrated consistent protective effects of higher educational attainment (EA) on the risk of suffering mental health conditions (MHC). Determining whether these beneficial effects are causal is challenging given the potential role of dynastic effects and demographic factors (assortative mating and population structure) in this association.

Objective: To evaluate to what extent the relationship between EA and various MHC is independent from dynastic effects and demographic factors.

Mapping associations of polygenic scores with autistic and ADHD traits in a single city region.

Background: The genetic and environmental aetiology of autistic and Attention Deficit Hyperactivity Disorder (ADHD) traits is known to vary spatially, but does this translate into variation in the association of specific common genetic variants?

Methods: We mapped associations between polygenic scores for autism and ADHD and their respective traits in the Avon Longitudinal Study of Parents and Children (N = 4,255-6,165) across the area surrounding Bristol, UK, and compared them to maps of environments associated with the prevalence of autism and ADHD.

Results: Our results suggest genetic associations vary spatially, with consistent patterns for autistic traits across polygenic scores constructed at different p-value thresholds. Patterns for ADHD traits were more variable across thresholds.

The role of body image dissatisfaction in the relationship between body size and disordered eating and self-harm: complimentary Mendelian randomization and mediation analyses.

Disordered eating and self-harm commonly co-occur in young people suggesting potential for shared underlying causes. Body image dissatisfaction (BID) has been recognised as a psychological correlate of body size, associated with both disordered eating and self-harm. However, the investigation into etiological pathways early in the lifecourse to provide detail on how body size and BID may foster disordered eating and self-harm remains largely unexplored.

Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with 'cigarette smoking initiation' really capturing?

Genetic variants used as instruments for exposures in Mendelian randomisation (MR) analyses may have horizontal pleiotropic effects (i.e., influence outcomes via pathways other than through the exposure), which can undermine the validity of results.

Epigenetic Aging and Racialized, Economic, and Environmental Injustice: NIMHD Social Epigenomics Program.

Importance: Epigenetic age acceleration is associated with exposure to social and economic adversity and may increase the risk of premature morbidity and mortality. However, no studies have included measures of structural racism, and few have compared estimates within or across the first and second generation of epigenetic clocks.

Objective: To determine whether epigenetic age acceleration is positively associated with exposures to diverse measures of racialized, economic, and environmental injustice measured at different levels and time periods.

Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank.

Background: Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.

Methods: We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; n=51 929; n=39 980) and subsequent arterial ischemic stroke (AIS; n=45 120; n=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank.