Type

Journal Article

Authors

Gary Donohoe
Derek W Morris
David O Mothersill
Michael Gill
Aiden Corvin
Denise Harold
Laura Whitton
Donna Cosgrove
Jessica F. Holland

Subjects

Psychiatry

Topics
genetic loci psychotic disorders rc0321 neuroscience biological psychiatry neuropsychiatry genome wide association studies regression analysis complement c4 psychology cognitive psychology

Beyond C4: Analysis of the complement gene pathway shows enrichment for IQ in patients with psychotic disorders and healthy controls (2019)

Abstract Variation in cognitive performance, which strongly predicts functional outcome in schizophrenia (SZ), has been associated with multiple immune‐relevant genetic loci. These loci include complement component 4 (C4A), structural variation at which was recently associated with SZ risk and synaptic pruning during neurodevelopment and cognitive function. Here, we test whether this genetic association with cognition and SZ risk is specific to C4A, or extends more broadly to genes related to the complement system. Using a gene‐set with an identified role in “complement” function (excluding C4A), we used MAGMA to test if this gene‐set was enriched for genes associated with human intelligence and SZ risk, using genome‐wide association summary statistics (IQ; N = 269 867, SZ; N = 105 318). We followed up this gene‐set analysis with a complement gene‐set polygenic score (PGS) regression analysis in an independent data set of patients with psychotic disorders and healthy participants with cognitive and genomic data (N = 1000). Enrichment analysis suggested that genes within the complement pathway were significantly enriched for genes associated with IQ, but not SZ. In a gene‐based analysis of 90 genes, SERPING1 was the most enriched gene for the phenotype of IQ. In a PGS regression analysis, we found that a complement pathway PGS associated with IQ genome‐wide association studies statistics also predicted variation in IQ in our independent sample. This association (observed across both patients and controls) remained significant after controlling for the relationship between C4A and cognition. These results suggest a robust association between the complement system and cognitive function, extending beyond structural variation at C4A.
Collections Ireland -> National College Ireland -> Subject = R Medicine: RC Internal medicine: RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Ireland -> National College Ireland -> Status = Published
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion: Psychology: Cognitive psychology
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion
Ireland -> National College Ireland -> Subject = R Medicine
Ireland -> National College Ireland -> Type = Article
Ireland -> National College Ireland -> Subject = B Philosophy. Psychology. Religion: Psychology
Ireland -> National College Ireland -> Subject = R Medicine: RC Internal medicine

Full list of authors on original publication

Gary Donohoe, Derek W Morris, David O Mothersill, Michael Gill, Aiden Corvin, Denise Harold, Laura Whitton, Donna Cosgrove, Jessica F. Holland

Experts in our system

1
Gary Donohoe
Trinity College Dublin
Total Publications: 162
 
2
Derek Morris
Trinity College Dublin
Total Publications: 168
 
3
David Mothersill
National College Ireland
Total Publications: 14
 
4
Michael Gill
Trinity College Dublin
Total Publications: 294
 
5
Aiden Corvin
Trinity College Dublin
Total Publications: 218
 
6
Denise Harold
Dublin City University
Total Publications: 11
 
7
Laura Whitton
National College Ireland
Total Publications: 4
 
8
Donna Cosgrove
National College Ireland
Total Publications: 10