A Large-Scale Genome-wide Association Study of Blood Pressure Accounting for Gene-Depressive Symptomatology Interactions in 564,680 Individuals from Diverse Populations.

Background Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample.

Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

Genomic structural equation modeling of reward-related traits: exploring the genetic factor structure and its relationship with psychopathology.

Reward sensitivity has a partial genetic background, and extreme levels may increase vulnerability to psychopathology. This study explores the genetic factor structure underlying reward-related traits and examines how genetic variance links to psychopathology. We modeled GWAS data from ten reward-related traits: risk tolerance (N = 975,353), extraversion (N = 122,886), sensation seeking (N = 132,395), (lack of) premeditation (N = 132,667), (lack of) perseverance (N = 133,517), positive urgency (N = 132,132), negative urgency (N = 132,559), attentional impulsivity (N = 124,739), motor impulsivity (N = 124,104), and nonplanning impulsivity (N = 123,509) to derive their genetic factor structure.

Familial co-aggregation and shared familiality among neurodevelopmental problems and with aggressive behavior, depression, anxiety, and substance use.

Objective: To refine the knowledge on familial transmission, we examined the (shared) familial components among neurodevelopmental problems (i.e. two attention-deficit/hyperactivity-impulsivity disorder [ADHD] and six autism spectrum disorder [ASD] subdomains) and with aggressive behavior, depression, anxiety, and substance use.

Lifestyle factors and incident multimorbidity related to chronic disease: a population-based cohort study.

Background: Multimorbidity is linked to poor quality of life, and increased healthcare costs, and multimorbidity risk is potentially mitigated by a healthy lifestyle. This study evaluated the individual and joint contributions of an extensive set of lifestyle factors to the development of multimorbidity.

Methods: A prospective study of 133,719 adults (age 45.

Positive and negative affect, related mental health traits, and cognitive performance: shared genetic architecture and potential causality.

Altered affect and cognitive dysfunction are transdiagnostic, burdensome, and pervasive features of many psychiatric conditions which remain poorly understood and have few efficacious treatments. Research on the genetic architecture of these phenotypes and causal relationships between them may provide insight into their aetiology and comorbidity. Using data from the Lifelines Cohort Study, we conducted genome-wide association studies (GWAS) on positive and negative affect and four cognitive domains (working memory, reaction time, visual learning and memory, executive function).

The contribution of attention-deficit/hyperactivity disorder polygenic load to metabolic and cardiovascular health outcomes: a large-scale population and sibling study.

Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers.

Mediating pathways between attention deficit hyperactivity disorder and type 2 diabetes mellitus: evidence from a two-step and multivariable Mendelian randomization study.

Aims: Type 2 diabetes (T2D) is a global health burden, more prevalent among individuals with attention deficit hyperactivity disorder (ADHD) compared to the general population. To extend the knowledge base on how ADHD links to T2D, this study aimed to estimate causal effects of ADHD on T2D and to explore mediating pathways.

Methods: We applied a two-step, two-sample Mendelian randomization (MR) design, using single nucleotide polymorphisms to genetically predict ADHD and a range of potential mediators.

Diet Quality at 3 Years of Age Relates to Lower Body Mass Index but Not Lower Blood Pressure at 10 Years of Age.

A healthy diet prevents overweight problems and hypertension. We investigated the associations of a healthy diet with the body mass index (BMI) and blood pressure (BP) in early childhood. In the GECKO birth cohort, height, weight, and BP were measured at 5 and 10 years of age.

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.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

Pathway-Based Mendelian Randomization for Pre-Infection IL-6 Levels Highlights Its Role in Coronavirus Disease.

Objectives: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19.

Prioritization of Kidney Cell Types Highlights Myofibroblast Cells in Regulating Human Blood Pressure.

Introduction: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

Methods: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney.

Alterations of gut microbiota and its metabolomics in children with 6PPDQ, PBDE, PCB, and metal(loid) exposure.

The composition and metabolites of the gut microbiota can be altered by environmental pollutants. However, the effect of co-exposure to multiple pollutants on the human gut microbiota has not been sufficiently studied. In this study, gut microorganisms and their metabolites were compared between 33 children from Guiyu, an e-waste dismantling and recycling area, and 34 children from Haojiang, a healthy environment.

Associations between autistic and comorbid somatic problems of gastrointestinal disorders, food allergy, pain, and fatigue in adults.

Autistic children frequently often have accompanying physical health problems. However, this has been much less studied in autistic men and women during adulthood.This is one of the first studies to investigate the associations between autistic and somatic problems in adults from the general population.