@article{e216e612b8134655b99e056c4832c462,
title = "Genetic schizophrenia risk variants jointly modulate total brain and white matter volume",
abstract = "Background: Thousands of common single nucleotide polymorphisms (SNPs) are weakly associated with schizophrenia. It is likely that subsets of disease-associated SNPs are associated with distinct heritable disease-associated phenotypes. Therefore, we examined the shared genetic susceptibility modulating schizophrenia and brain volume. Methods: Odds ratios for genome-wide SNP data were calculated in the sample collected by the Psychiatric Genome-wide Association Study Consortium (8690 schizophrenia patients and 11,831 control subjects, excluding subjects from the present study). These were used to calculate individual polygenic schizophrenia (risk) scores in an independent sample of 152 schizophrenia patients and 142 healthy control subjects with available structural magnetic resonance imaging scans. Results: In the entire group, the polygenic schizophrenia score was significantly associated with total brain volume (R2=.048, p=1.6×10-4) and white matter volume (R2=.051, p=8.6×10-5) equally in patients and control subjects. The number of (independent) SNPs that substantially influenced both disease risk and white matter (n=2020) was much smaller than the entire set of SNPs that modulated disease status (n=14,751). From the set of 2020 SNPs, a group of 186 SNPs showed most evidence for association with white matter volume and an explorative functional analysis showed that these SNPs were located in genes with neuronal functions. Conclusions: These results indicate that a relatively small subset of schizophrenia genetic risk variants is related to the (normal) development of white matter. This, in turn, suggests that disruptions in white matter growth increase the susceptibility to develop schizophrenia.",
keywords = "Endophenotype, SNPs, genome-wide, imaging, psychiatric, structural MRI",
author = "{Psychiatric Genome-wide association study (GWAS) Consortium} and {Terwisscha Van Scheltinga}, {Afke F.} and Bakker, {Steven C.} and {Van Haren}, {Neeltje E.M.} and Derks, {Eske M.} and Buizer-Voskamp, {Jacobine E.} and Boos, {Heleen B.M.} and Wiepke Cahn and {Hulshoff Pol}, {Hilleke E.} and Stephan Ripke and Ophoff, {Roel A.} and Kahn, {Ren{\'e} S.} and Stephan Ripke and Sanders, {Alan R.} and Kendler, {Kenneth S.} and Levinson, {Douglas F.} and Pamela Sklar and Holmans, {Peter A.} and Lin, {Dan Yu} and Jubao Duan and Ophoff, {Roel A.} and Andreassen, {Ole A.} and Edward Scolnick and Sven Cichon and {St. Clair}, David and Aiden Corvin and Hugh Gurling and Thomas Werge and Dan Rujescu and Blackwood, {Douglas H.R.} and Pato, {Carlos N.} and Malhotra, {Anil K.} and Shaun Purcell and Frank Dudbridge and Neale, {Benjamin M.} and Lizzy Rossin and Visscher, {Peter M.} and Danielle Posthuma and Ruderfer, {Douglas M.} and Ayman Fanous and Hreinn Stefansson and Stacy Steinberg and Mowry, {Bryan J.} and Vera Golimbet and {De Hert}, Marc and J{\"o}nsson, {Erik G.} and Istv{\'a}n Bitter and Pietil{\"a}inen, {Olli P.H.} and Collier, {David A.} and Sarah Tosato and Ingrid Agartz and Margot Albus and Madeline Alexander and Amdur, {Richard L.} and Farooq Amin and Nicholas Bass and Bergen, {Sarah E.} and Black, {Donald W.} and B{\o}rglum, {Anders D.} and Brown, {Matthew A.} and Richard Bruggeman and Buccola, {Nancy G.} and Byerley, {William F.} and Wiepke Cahn and Cantor, {Rita M.} and Carr, {Vaughan J.} and Catts, {Stanley V.} and Khalid Choudhury and Cloninger, {C. Robert} and Paul Cormican and Nicholas Craddock and Danoy, {Patrick A.} and Susmita Datta and {de Haan}, Lieuwe and Ditte Demontis and Dimitris Dikeos and Srdjan Djurovic and Peter Donnelly and Gary Donohoe and Linh Duong and Sarah Dwyer and Anders Fink-Jensen and Robert Freedman and Freimer, {Nelson B.} and Marion Friedl and Lyudmila Georgieva and Ina Giegling and Michael Gill and Birte Glenth{\o}j and Stephanie Godard and Marian Hamshere and Mark Hansen and Thomas Hansen and Hartmann, {Annette M.} and Henskens, {Frans A.} and Hougaard, {David M.} and Hultman, {Christina M.} and Andr{\'e}s Ingason and Jablensky, {Assen V.} and Jakobsen, {Klaus D.} and Maurice Jay and Gesche J{\"u}rgens and Kahn, {Ren{\'e} S.} and Keller, {Matthew C.} and Gunter Kenis and Elaine Kenny and Yunjung Kim and Kirov, {George K.} and Heike Konnerth and Bettina Konte and Lydia Krabbendam and Robert Krasucki and Lasseter, {Virginia K.} and Claudine Laurent and Jacob Lawrence and Todd Lencz and Lerer, {F. Bernard} and Liang, {Kung Yee} and Paul Lichtenstein and Lieberman, {Jeffrey A.} and Linszen, {Don H.} and Jouko L{\"o}nnqvist and Loughland, {Carmel M.} and Maclean, {Alan W.} and Maher, {Brion S.} and Wolfgang Maier and Jacques Mallet and Pat Malloy and Manuel Mattheisen and Morten Mattingsdal and McGhee, {Kevin A.} and McGrath, {John J.} and Andrew McIntosh and McLean, {Duncan E.} and Andrew McQuillin and Ingrid Melle and Michie, {Patricia T.} and Vihra Milanova and Morris, {Derek W.} and Ole Mors and Mortensen, {Preben B.} and Valentina Moskvina and Pierandrea Muglia and Inez Myin-Germeys and Nertney, {Deborah A.} and Gerald Nestadt and Jimmi Nielsen and Ivan Nikolov and Merete Nordentoft and Nadine Norton and N{\"o}then, {Markus M.} and O{\textquoteright}Dushlaine, {Colm T.} and Ann Olincy and Line Olsen and O{\textquoteright}Neill, {F. Anthony} and {\o}rntoft, {Torben F.} and Owen, {Michael J.} and Christos Pantelis and George Papadimitriou and Pato, {Michele T.} and Leena Peltonen and Hannes Petursson and Ben Pickard and Jonathan Pimm and Pulver, {Ann E.} and Vinay Puri and Digby Quested and Quinn, {Emma M.} and Rasmussen, {Henrik B.} and R{\'e}thelyi, {J{\'a}nos M.} and Robert Ribble and Marcella Rietschel and Riley, {Brien P.} and Mirella Ruggeri and Ulrich Schall and Schulze, {Thomas G.} and Schwab, {Sibylle G.} and Scott, {Rodney J.} and Jianxin Shi and Engilbert Sigurdsson and Silverman, {Jeremy M.} and Spencer, {Chris C.A.} and Kari Stefansson and Amy Strange and Eric Strengman and Stroup, {T. Scott} and Jaana Suvisaari and Lars Terenius and Srinivasa Thirumalai and Thygesen, {Johan H.} and Sally Timm and Draga Toncheva and {van den Oord}, Edwin and {van Os}, Jim and {van Winkel}, Ruud and Jan Veldink and Dermot Walsh and Wang, {August G.} and Durk Wiersma and Wildenauer, {Dieter B.} and Williams, {Hywel J.}",
note = "Funding Information: This work was supported by a Veni grant from Zorg Onderzoek Nederland, Medische Wetenschappen to SCB (the Dutch organization for health research and development, project number: 91686137), by a grant from the Dutch Brain Foundation to SCB [Grant 14F06(2)-34], and by Top Institute Pharma (project T5-203). The Genetic Risk and Outcome of Psychosis project was supported by a Grant from Zorg Onderzoek Nederland, Medische Wetenschappen, within the Mental Health program (project number: 10.000.1001). Genome-wide association study of this sample was funded by the National Institute of Mental Health (Grant RO1 MG078075 to RAO). ",
year = "2013",
month = mar,
day = "15",
doi = "10.1016/j.biopsych.2012.08.017",
language = "English",
volume = "73",
pages = "525--531",
journal = "Biological Psychiatry",
issn = "0006-3223",
number = "6",
}