Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe
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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, Ditte; Steffens, M; Strohmaier, J; Haenisch, B; Breuer, R; Czerski, P M; Giegling, I; Strengman, E; Schmael, C; Mors, Ole; Mortensen, P B; Hougaard, D M; Orntoft, T; Kapelski, P; Priebe, L; Basmanav, F B; Forstner, A J; Hoffmann, Pablo Francisco F.; 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, Robert; 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; Clair, David St; Hansen, T.; Ingason, A.; Jakobsen, Klaus D; Duong, L.; Werge, T.; Melle, Ingrid; Andreassen, Ole A; Djurovic, Srdjan; Bitter, István; Réthelyi, János M; Abramova, Lilia; Kaleda, Vasily; Golimbet, Vera; Jönsson, Erik G; Terenius, L.; Agartz, Ingrid; Winkel, Ruud van; Kenis, Gunter; Hert, Marc De; Veldink, Jan; Wiuf, Carsten; Didriksen, Michael; Craddock, N; Owen, M J; O'Donovan, M C; Børglum, Anders; Rujescu, D; Walter, H; Meyer-Lindenberg, A; Nöthen, M M; Ophoff, R A; Cichon, S.
In: Molecular Psychiatry, Vol. 17, No. 9, 2012, p. 906-917.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe
AU - Rietschel, M
AU - Mattheisen, M
AU - Degenhardt, F
AU - Kahn, René S
AU - Linszen, Don H
AU - Os, Jim van
AU - Wiersma, Durk
AU - Bruggeman, Richard
AU - Cahn, Wiepke
AU - de Haan, Lieuwe
AU - Krabbendam, Lydia
AU - Myin-Germeys, Inez
AU - Mühleisen, T W
AU - Kirsch, P
AU - Esslinger, C
AU - Herms, S
AU - Demontis, Ditte
AU - Steffens, M
AU - Strohmaier, J
AU - Haenisch, B
AU - Breuer, R
AU - Czerski, P M
AU - Giegling, I
AU - Strengman, E
AU - Schmael, C
AU - Mors, Ole
AU - Mortensen, P B
AU - Hougaard, D M
AU - Orntoft, T
AU - Kapelski, P
AU - Priebe, L
AU - Basmanav, F B
AU - Forstner, A J
AU - Hoffmann, Pablo Francisco F.
AU - Meier, S
AU - Nikitopoulos, J
AU - Moebus, S
AU - Alexander, M
AU - Mössner, R
AU - Wichmann, H-E
AU - Schreiber, S
AU - Rivandeneira, F
AU - Hofman, A
AU - Uitterlinden, A G
AU - Wienker, T F
AU - Schumacher, J
AU - Hauser, J
AU - Maier, W
AU - Cantor, Robert
AU - Erk, S
AU - Schulze, T G
AU - Stefansson, Hreinn
AU - Steinberg, Stacy
AU - Gustafsson, Omar
AU - Sigurdsson, Engilbert
AU - Petursson, Hannes
AU - Kong, Augustine
AU - Stefansson, Kari
AU - Pietiläinen, Olli P H
AU - Tuulio-Henriksson, Annamari
AU - Paunio, Tiina
AU - Lonnqvist, Jouko
AU - Suvisaari, Jaana
AU - Peltonen, Leena
AU - Ruggeri, Mirella
AU - Tosato, Sarah
AU - Walshe, Muriel
AU - Murray, Robin
AU - Collier, David A
AU - Clair, David St
AU - Hansen, T.
AU - Ingason, A.
AU - Jakobsen, Klaus D
AU - Duong, L.
AU - Werge, T.
AU - Melle, Ingrid
AU - Andreassen, Ole A
AU - Djurovic, Srdjan
AU - Bitter, István
AU - Réthelyi, János M
AU - Abramova, Lilia
AU - Kaleda, Vasily
AU - Golimbet, Vera
AU - Jönsson, Erik G
AU - Terenius, L.
AU - Agartz, Ingrid
AU - Winkel, Ruud van
AU - Kenis, Gunter
AU - Hert, Marc De
AU - Veldink, Jan
AU - Wiuf, Carsten
AU - Didriksen, Michael
AU - Craddock, N
AU - Owen, M J
AU - O'Donovan, M C
AU - Børglum, Anders
AU - Rujescu, D
AU - Walter, H
AU - Meyer-Lindenberg, A
AU - Nöthen, M M
AU - Ophoff, R A
AU - Cichon, S
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1038/mp.2011.80
DO - 10.1038/mp.2011.80
M3 - Journal article
C2 - 21747397
VL - 17
SP - 906
EP - 917
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 9
ER -
ID: 40204903