TY - JOUR
T1 - Cortical patterning of abnormal morphometric similarity in psychosis is associated with brain expression of schizophrenia-related genes
AU - Morgan, Sarah E.
AU - Seidlitz, Jakob
AU - Whitaker, Kirstie J.
AU - Romero-Garcia, Rafael
AU - Clifton, Nicholas E.
AU - Scarpazza, Cristina
AU - van Amelsvoort, Therese
AU - Marcelis, Machteld
AU - van Os, Jim
AU - Donohoe, Gary
AU - Mothersill, David
AU - Corvin, Aiden
AU - Pocklington, Andrew
AU - Raznahan, Armin
AU - McGuire, Philip
AU - Vértes, Petra E.
AU - Bullmore, Edward T.
AU - Morgan, Sarah
PY - 2019/5/7
Y1 - 2019/5/7
N2 - Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case–control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case–control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case–control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologi-cally relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.
AB - Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case–control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case–control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case–control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologi-cally relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.
KW - Allen Human Brain Atlas
KW - Dysconnectivity
KW - Morphometric similarity
KW - Network neuroscience
KW - Psychosis
U2 - 10.1073/pnas.1820754116
DO - 10.1073/pnas.1820754116
M3 - Article
C2 - 31004051
AN - SCOPUS:85065662406
SN - 0027-8424
VL - 116
SP - 9604
EP - 9609
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -