Type

Journal Article

Authors

D W Morris
M Gill
L Gallagher
G Donohoe
A P Corvin
R Anney
D Tropea
S Ennis
E Kelleher
C Fahey
and 5 others

Subjects

Psychiatry

Topics
loss variants genes rare pathology schizophrenia and disorders autism spectrum disorders neural cell adhesion molecules

Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. (2012)

Abstract Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

D W Morris, M Gill, L Gallagher, G Donohoe, A P Corvin, R Anney, D Tropea, S Ennis, E Kelleher, C Fahey and 5 others

Experts in our system

1
Derek Morris
Trinity College Dublin
Total Publications: 150
 
2
Michael Gill
Trinity College Dublin
Total Publications: 260
 
3
Louise Gallagher
Trinity College Dublin
Total Publications: 55
 
4
Gary Donohoe
Trinity College Dublin
Total Publications: 130
 
5
Aiden Corvin
Trinity College Dublin
Total Publications: 190
 
6
Richard Anney
Trinity College Dublin
Total Publications: 38
 
7
Daniela Tropea
Trinity College Dublin
Total Publications: 25
 
8
Sean Ennis
University College Dublin
Total Publications: 52
 
9
Ciara Fahey
Trinity College Dublin
Total Publications: 30