Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders, 2019, Smoller et al

Andy · Mar 9, 2020

Highlights

Three groups of highly genetically-related disorders among 8 psychiatric disorders

Identified 109 pleiotropic loci affecting more than one disorder

Pleiotropic genes show heightened expression beginning in 2nd prenatal trimester

Pleiotropic genes play prominent roles in neurodevelopmental processes

Summary
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/hyperactivity 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.
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Open access, https://www.cell.com/cell/fulltext/S0092-8674(19)31276-0

Summary: The largest genetic map of mental health disorders to date reveals there are three groups of highly genetically related disorders among eight psychiatric disorders. A gene related to nervous system development is a risk factor for all eight disorders studied. The RBFOX1 gene is implicated in seven of the eight disorders. ADHD and depression share 44% of genetic risk factors common in the general population. 109 pleiotropic loci affect more than one disorder. These pleiotropic loci are within genes that show heightened expression in the brain through the lifespan, beginning during the second trimester of pregnancy.

Source: University of Barcelona

An international study published in the journal Cell, has described 109 genetic variants associated with eight psychiatric disorders: autism, ADHD, schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder and Tourette Syndrome, in a total of about 230,000 patients worldwide.
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https://neurosciencenews.com/genetics-mental-health-map-15880/

Snow Leopard · Mar 10, 2020

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Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders, 2019, Smoller et al

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Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders, 2019, Smoller et al

Andy Retired committee member

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