@article{10902/16308,
year = {2016},
url = {http://hdl.handle.net/10902/16308},
abstract = {Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.},
organization = {This work was supported by R01 HG 006855 (to S.A.M), by the Stanley Center for Psychiatric Research (to S.A.M and B.S.), by R01 MH077139 (to the PGC), and by T32 GM007753 (to A.S. and M.B.).},
publisher = {Nature Publishing Group},
publisher = {Nature. 2016 Feb 11;530(7589):177-83},
title = {Schizophrenia risk from complex variation of complement component 4},
author = {Sekar, Aswin and Bialas, Allison R. and Rivera, Heather de and Davis, Avery and Hammond, Timothy R. and Kamitaki, Nolan and Tooley, Katherine and Presumey, Jessy and Baum, Matthew and Van Doren, Vanessa and Genovese, Giulio and Rose, Samuel A. and Handsaker, Robert E. and Schizophrenia Working Group of the Psychiatric Genomics Consortium and Daly, Mark J. and Carroll, Michael C. and Stevens, Beth and McCarroll, Steven A. and Crespo Facorro, Benedicto},
}