Journal Article


G Donohoe
D W Morris
A Corvin
M Gill
M C O'Donovan
M Owen
K Mantripragada
A Richards
T Petryshen
G Blokland
and 6 others



genome wide association schizophrenia cognitive functions mir patients spatial working memory controls cognitive

MiR-137-derived polygenic risk: effects on cognitive performance in patients with schizophrenia and controls. (2016)

Abstract Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression. This list was cross-referenced with genome-wide schizophrenia association data to construct individual polygenic scores. We then tested, in a sample of 808 patients and 192 controls, whether these risk scores were associated with altered performance on cognitive functions known to be affected in schizophrenia. A subgroup of healthy participants also underwent functional imaging during memory (n=108) and face processing tasks (n=83). Increased polygenic risk within the empirically derived miR-137 regulated gene score was associated with significantly lower performance on intelligence quotient, working memory and episodic memory. These effects were observed most clearly at a polygenic threshold of P=0.05, although significant results were observed at all three thresholds analyzed. This association was found independently for the gene set as a whole, excluding the schizophrenia-associated MIR137 SNP itself. Analysis of the spatial working memory fMRI task further suggested that increased risk score (thresholded at P=10(-5)) was significantly associated with increased activation of the right inferior occipital gyrus. In conclusion, these data are consistent with emerging evidence that MIR137 associated risk for schizophrenia may relate to its broader downstream genetic effects.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

G Donohoe, D W Morris, A Corvin, M Gill, M C O'Donovan, M Owen, K Mantripragada, A Richards, T Petryshen, G Blokland and 6 others

Experts in our system

Gary Donohoe
Trinity College Dublin
Total Publications: 143
Derek Morris
Trinity College Dublin
Total Publications: 156
Aiden Corvin
Trinity College Dublin
Total Publications: 199
Michael Gill
Trinity College Dublin
Total Publications: 273
Michael C O'Donovan
Trinity College Dublin
Total Publications: 19
Michael J. Owen
Trinity College Dublin
Total Publications: 20
Kiran Mantripragada
Dublin City University
Total Publications: 5
Alex Richards
Dublin City University
Total Publications: 6