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 accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study.

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806).

Randomized controlled trials comparing gastric bypass, gastric band, and sleeve gastrectomy: A systematic review examining validity and applicability to wider clinical practice.

Consideration of how applicable the results of surgical trials are to clinical practice is important to inform decision-making. Randomized controlled trials comparing at least two surgical interventions (of gastric bypass, gastric band, and sleeve gastrectomy) for severe and complex obesity were examined using the PRagmatic Explanatory Continuum Indicator Summary-2 tool, to consider how applicable the trial results are to clinical practice, and the Risk of Bias 2 tool, to examine validity. MEDLINE, Embase, and CENTRAL databases were searched for studies published between November 2013 and June 2021, and 15 were identified.

Efficacy of metformin targets on cardiometabolic health in the general population and non-diabetic individuals: a Mendelian randomization study.

Background: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR).

A narrative review of recent tools and innovations toward automating living systematic reviews and evidence syntheses.

Living reviews are an increasingly popular research paradigm. The purpose of a 'living' approach is to allow rapid collation, appraisal and synthesis of evolving evidence on an important research topic, enabling timely influence on patient care and public health policy. However, living reviews are time- and resource-intensive.

Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects.

Association between inflammation and cognition: Triangulation of evidence using a population-based cohort and Mendelian randomization analyses.

Background: Inflammation is associated with cognitive functioning and dementia in older adults, but whether inflammation is related to cognitive functioning in youth and whether these associations are causal remains unclear.

Methods: In a population-based cohort (Avon Longitudinal Study of Parents and Children; ALSPAC), we investigated cross-sectional associations of inflammatory markers (C-reactive protein [CRP], Interleukin-6 [IL-6] and Glycoprotein acetyls [GlycA]) with measures of cold (working memory, response inhibition) and hot (emotion recognition) cognition at age 24 (N = 3,305 in multiple imputation models). Furthermore, we conducted one-sample and two-sample bidirectional Mendelian randomization (MR) analyses to examine potential causal effects of genetically-proxied inflammatory markers (CRP, GlycA, IL-6, IL-6 receptor, soluble IL-6 receptor) on cognitive measures (above) and on general cognitive ability.

Associations between emotion recognition and autistic and callous-unemotional traits: differential effects of cueing to the eyes.

Background: Although autism and callous-unemotional (CU) traits are distinct conditions, both are associated with difficulties in emotion recognition. However, it is unknown whether the emotion recognition difficulties characteristic of autism and CU traits are driven by comparable underpinning mechanisms.

Methods: We tested whether cueing to the eyes improved emotion recognition in relation to autistic and CU traits in a heterogeneous sample of children enhanced for social, emotional and behavioural difficulties.

Associations of negative affective biases and depressive symptoms in a community-based sample.

Background: Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample, followed by examining differences between remitted individuals and controls.

Relationship between change in social evaluation learning and mood in early antidepressant treatment: A prospective cohort study in primary care.

Background: Antidepressants are proposed to work by increasing sensitivity to positive versus negative information. Increasing positive affective learning within social contexts may help remediate negative self-schema. We investigated the association between change in biased learning of social evaluations about the self and others, and mood during early antidepressant treatment.

Mapping the genetic and environmental aetiology of autistic traits in Sweden and the United Kingdom.

Background: Autistic traits are influenced by both genetic and environmental factors, and are known to vary geographically in prevalence. But to what extent does their aetiology also vary from place to place?

Methods: We applied a novel spatial approach to data on autistic traits from two large twin studies, the Child and Adolescent Twin Study in Sweden (CATSS;  = 16,677, including 8307 twin pairs) and the Twins Early Development Study in the UK (TEDS;  = 11,594, including 5796 twin pairs), to explore how the influence of nature and nurture on autistic traits varies from place to place.

Results: We present maps of gene- and environment- by geography interactions in Sweden and the United Kingdom (UK), showing geographical variation in both genetic and environmental influences across the two countries.

Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity.

Background: Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries.

Methods: In this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry.

Objective measures of reward sensitivity and motivation in people with high low anhedonia.

Background: Anhedonia - a diminished interest or pleasure in activities - is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive.

Keeping up with the Wangs: individual and contextual influences on mental wellbeing and depressive symptoms in China.

Background: In recent decades, China has experienced dramatic changes to its social and economic environment, which has affected the distribution of wellbeing across its citizens. While several studies have investigated individual level predictors of wellbeing in the Chinese population, less research has been done looking at contextual effects. This cross-sectional study looks at the individual and contextual effects of (regional) education, unemployment and marriage (rate) on individual happiness, life satisfaction and depressive symptomatology.

Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis.

Background: Glycemic traits-such as hyperinsulinemia, hyperglycemia, and type 2 diabetes-have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type 2 diabetes with colorectal cancer.

Methods: Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type 2 diabetes (n = 268).

Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.

Background: Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis.

Epigenetic Regulation of Associates With Myocardial Infarction and Platelet Function.

Background: DNA hypomethylation at the (F2R like thrombin or trypsin receptor 3) locus has been associated with both smoking and atherosclerotic cardiovascular disease; whether these smoking-related associations form a pathway to disease is unknown. encodes protease-activated receptor 4, a potent thrombin receptor expressed on platelets. Given the role of thrombin in platelet activation and the role of thrombus formation in myocardial infarction, alterations to this biological pathway could be important for ischemic cardiovascular disease.