Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

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Risks of acute kidney injury according to the acute kidney injury network criteria.

<p>Risks of acute kidney injury according to the acute kidney injury network criteria.</p

Patient and procedure characteristics.

<p>Patient and procedure characteristics.</p

Whether a hydration strategy is cost-effective, depends on how much one is willing to pay (WTP) (in US dollars) to avoid one case of CI-AKI.

<p>This figure shows the probability that one-hour hydration with sodium bicarbonate prior to intra-arterial contrast administration is cost-effective compared with periprocedural saline hydration.</p

Trial profile.

<p>Trial profile.</p

Randomized trial of one-hour sodium bicarbonate vs standard periprocedural saline hydration in chronic kidney disease patients undergoing cardiovascular contrast procedures - Fig 2

<p><b>A)</b> Subgroup analyses on the primary outcome of a relative increase in serum creatinine 48–96 hours post intra-arterial contrast administration. Effect size is calculated as the difference in the mean relative increase in serum creatinine between both randomisation groups. <b>B)</b> Subgroup analyses on the secondary outcome of risk of contrast-induced acute kidney injury, calculated as relative risk. The straight line indicates the point estimate of the entire study population and the dashed line indicates no effect. Baseline creatinine clearance was calculated using the MDRD-formula.</p

Estimated hospital costs per patient between randomisation and two months follow-up.

<p>Estimated hospital costs per patient between randomisation and two months follow-up.</p