Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe

Rietschel, M., Mattheisen, M., Degenhardt, F., Kahn, René S, Linszen, Don H., Os, Jim van, Wiersma, Durk, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Krabbendam, Lydia, Myin-Germeys, Inez, Mühleisen, T. W., Kirsch, P., Esslinger, C., Herms, S., Demontis, D., Steffens, M., Strohmaier, J., Haenisch, B., Breuer, R., Czerski, P. M., Giegling, I., Strengman, E., Schmael, C., Mors, O., Mortensen, P. B., Hougaard, D. M., Ørntoft, T., Kapelski, P., Priebe, L., Basmanav, F. B., Forstner, A. J., Hoffmann, P., Meier, S., Nikitopoulos, J., Moebus, S., Alexander, M., Mössner, R., Wichmann, H.-E., Schreiber, S., Rivandeneira, F., Hofman, A., Uitterlinden, A. G., Wienker, T. F., Schumacher, J., Hauser, J., Maier, W., Cantor, R. M., Erk, S.., Schulze, T. G., Stefansson, Hreinn, Steinberg, Stacy, Gustafsson, Omar, Sigurdsson, Engilbert, Petursson, Hannes, Kong, Augustine, Stefansson, Kari, Pietiläinen, Olli P. H., Tuulio-Henriksson, Annamari, Paunio, Tiina, Lonnqvist, Jouko, Suvisaari, Jaana, Peltonen, Leena, Ruggeri, Mirella, Tosato, Sarah, Walshe, Muriel, Murray, Robin, Collier, David A., St. Clair, David, Hansen, Thomas, Ingason, Andres, Jakobsen, Klaus D., Duong, Linh, Werge, Thomas, Melle, Ingrid, Andreassen, Ole A., Djurovic, Srdjan, Bitter, István, Réthelyi, János M., Abramova, Lilia, Kaleda, Vasily, Golimbet, Vera, Jönsson, Erik G., Terenius, Lars, Agartz, Ingrid, Winkel, Ruud van, Kenis, Gunter, Hert, Marc De, Veldink, Jan, Wiuf, Carsten, Didriksen, Michael, Craddock, Nicholas John, Owen, Michael John, O'Donovan, Michael Conlon, Børglum, A. D., Rujescu, D., Walter, H., Meyer-Lindenberg, A., Nöthen, M. M., Ophoff, R. A. and Cichon, S. 2011. Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe. Molecular Psychiatry , pp. 1-12. 10.1038/mp.2011.80

Full text not available from this repository.

Abstract

Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10−9, odds ratio (OR)=1.25). This finding was replicated in 23 206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RZ Other systems of medicine
Uncontrolled Keywords: common variation; genome-wide association study; GWAS; imaging genetics; schizophrenia
Additional Information: Advance online publication
ISSN: 1359-4184
Last Modified: 04 Jun 2017 03:59
URI: http://orca.cf.ac.uk/id/eprint/30199

Citation Data

Cited 64 times in Google Scholar. View in Google Scholar

Cited 74 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item