dc.contributor.author |
Takata, Atsushi
|
|
dc.contributor.author |
Xu, Bin
|
|
dc.contributor.author |
Ionita-Laza, Iuliana
|
|
dc.contributor.author |
Roos, J.L. (Johannes Louw)
|
|
dc.contributor.author |
Gogos, Joseph A.
|
|
dc.contributor.author |
Karayiorgou, Maria
|
|
dc.date.accessioned |
2015-09-10T06:35:29Z |
|
dc.date.available |
2015-09-10T06:35:29Z |
|
dc.date.issued |
2014-05 |
|
dc.description.abstract |
Loss-of-function (LOF) (i.e., nonsense, splice site,
and frameshift) variants that lead to disruption of
gene function are likely to contribute to the etiology
of neuropsychiatric disorders. Here, we perform a
systematic investigation of the role of both de novo
and inherited LOF variants in schizophrenia using
exome sequencing data from 231 case and 34 control
trios. We identify two de novo LOF variants in
the SETD1A gene, which encodes a subunit of histone
methyltransferase, a finding unlikely to have
occurred by chance, and provide evidence for a
more general role of chromatin regulators in schizophrenia
risk. Transmission pattern analyses reveal
that LOF variants are more likely to be transmitted
to affected individuals than controls. This is especially
true for private LOF variants in genes intolerant
to functional genetic variation. These findings highlight
the contribution of LOF mutations to the genetic
architecture of schizophrenia and provide important
insights into disease pathogenesis. |
en_ZA |
dc.description.librarian |
hb2015 |
en_ZA |
dc.description.sponsorship |
Partially supported by National Institute of Mental Health (NIMH) grants
MH061399 and MH097879.Lieber Center for Schizophrenia Research at Columbia University. Postdoctoral Fellowship for Research Abroad. Partially supported by a National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award. |
en_ZA |
dc.description.uri |
http://www.journals.elsevier.com/neuron |
en_ZA |
dc.identifier.citation |
Takata, A, Xu, B, Ionita-Laza, I, Roos, JL, Gogos, JA & Karayiorgou, M 2014, 'Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene', Neuron, vol. 82, no. 4, pp. 773-780. |
en_ZA |
dc.identifier.issn |
0896-6273 (print) |
|
dc.identifier.issn |
1097-4199 (online) |
|
dc.identifier.other |
10.1016/j.neuron.2014.04.043 |
|
dc.identifier.uri |
http://hdl.handle.net/2263/49761 |
|
dc.language.iso |
en |
en_ZA |
dc.publisher |
Elsevier |
en_ZA |
dc.rights |
© 2014 Elsevier Inc. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Neuron. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuron, vol. 82, no. 4, pp. 773-780, 2014. doi : 10.1016/j.neuron.2014.04.043. |
en_ZA |
dc.subject |
Loss of function variants |
en_ZA |
dc.subject |
Contribute |
en_ZA |
dc.subject |
Schizophrenia risk |
en_ZA |
dc.subject |
SETD1A |
en_ZA |
dc.subject |
Candidate |
en_ZA |
dc.subject |
Susceptibility gene |
en_ZA |
dc.subject |
Loss-of-function (LOF) |
en_ZA |
dc.title |
Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene |
en_ZA |
dc.type |
Postprint Article |
en_ZA |