Portal de Periódicos da CAPES

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

2011; Springer Nature; Volume: 17; Issue: 9 Linguagem: Inglês

10.1038/mp.2011.80

1476-5578

M. Rietschel, Manuel Mattheisen, F. Degenhardt, René S. Kahn, Don Linszen, Jim van Os, Durk Wiersma, Richard Bruggeman, Wiepke Cahn, Lieuwe de Haan, Lydia Krabbendam, Inez Myin‐Germeys, Thomas W. Mühleisen, Peter Kirsch, Christine Esslinger, Stefan Herms, Ditte Demontis, Michael Steffens, J Strohmaier, Britta Haenisch, René Breuer, Piotr M. Czerski, I Giegling, E Strengman, C Schmael, Ole Mors, Preben Bo Mortensen, D M Hougaard, Torben Ørntoft, Paweł Kapelski, Lutz Priebe, F B Basmanav, Andreas J. Forstner, Per Hoffmann, S Meier, J A. Nikitopoulos, Susanne Moebus, Michael P. Alexander, R Mössner, H-E Wichmann, S. Schreiber, Fernando Rivandeneira, A. Hofman, André G. Uitterlinden, T. F. Wienker, J Schumacher, J Hauser, W. Maier, R. M. Cantor, Susanne Erk, Thomas G. Schulze, Hreinn Stefánsson, Stacy Steinberg, Ómar Gústafsson, Engilbert Sigurðsson, Hannes Pétursson, Augustine Kong, Kári Stéfansson, Olli Pietiläinen, Annamari Tuulio‐Henriksson, Tiina Paunio, Jouko Lönnqvist, Jaana Suvisaari, Leena Peltonen, Mirella Ruggeri, Sarah Tosato, Muriel Walshe, Robin M. Murray, David Collier, David St Clair, Thomas Hansen, Andrés Ingason, Klaus D. Jakobsen, Linh Viet Duong, Thomas Werge, Ingrid Melle, Ole A. Andreassen, Srdjan Djurovic, István Bitter, János Réthelyi, Л. И. Абрамова, В. Г. Каледа, В. Е. Голимбет, Erik G. Jönsson, Lars Terenius, Ingrid Agartz, Ruud van Winkel, Günter Kenis, Marc D. Binder, Jan H. Veldink, Carsten Wiuf, Michael Didriksen, Nick Craddock, Michael J. Owen, Michael O’Donovan, Anders D. Børglum, Dan Rujescu, Henrik Walter, Andreas Meyer‐Lindenberg, Markus M. Nöthen, Roel A. Ophoff, Sven Cichon,

Genomics and Rare Diseases

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.