Cross-Disorder
Group of the Psychiatric Genomics Consortium, (collaborator
Oades,R.D.), Genomic
relationships, novel loci and pleiotropic mechanisms across eight psychiatric
disorders. 2019,
Cell, 179, 1469-1482.e11.
Abstract
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.
0/ 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.
1/ Genetic correlation analyses revealed
a meaningful structure within the eight disorders, identifying three
groups of inter-related disorders.
2/ 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.
3/ 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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