title: Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.
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.
authors: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. marcella.rietschel@zi-mannheim.de
authors: M
authors: M
authors: Rietschel
authors: M
authors: M
authors: Mattheisen
authors: F
authors: F
authors: Degenhardt
authors: T W
authors: TW
authors: Mühleisen
authors: P
authors: P
authors: Kirsch
authors: C
authors: C
authors: Esslinger
authors: S
authors: S
authors: Herms
authors: D
authors: D
authors: Demontis
authors: M
authors: M
authors: Steffens
authors: J
authors: J
authors: Strohmaier
authors: B
authors: B
authors: Haenisch
authors: R
authors: R
authors: Breuer
authors: P M
authors: PM
authors: Czerski
authors: I
authors: I
authors: Giegling
authors: E
authors: E
authors: Strengman
authors: C
authors: C
authors: Schmael
authors: O
authors: O
authors: Mors
authors: P B
authors: PB
authors: Mortensen
authors: D M
authors: DM
authors: Hougaard
authors: T
authors: T
authors: Ørntoft
authors: P
authors: P
authors: Kapelski
authors: L
authors: L
authors: Priebe
authors: F F
authors: FF
authors: Basmanav
authors: A J
authors: AJ
authors: Forstner
authors: P
authors: P
authors: Hoffman
authors: S
authors: S
authors: Meier
authors: J
authors: J
authors: Nikitopoulos
authors: S
authors: S
authors: Moebus
authors: M
authors: M
authors: Alexander
authors: R
authors: R
authors: Mössner
authors: H -E
authors: H-
authors: Wichmann
authors: S
authors: S
authors: Schreiber
authors: F
authors: F
authors: Rivandeneira
authors: A
authors: A
authors: Hofman
authors: A G
authors: AG
authors: Uitterlinden
authors: T F
authors: TF
authors: Wienker
authors: J
authors: J
authors: Schumacher
authors: J
authors: J
authors: Hauser
authors: W
authors: W
authors: Maier
authors: R M
authors: RM
authors: Cantor
authors: S
authors: S
authors: Erk
authors: T G
authors: TG
authors: Schulze
authors: N
authors: N
authors: Craddock
authors: M J
authors: MJ
authors: Owen
authors: M C
authors: MC
authors: O'Donovan
authors: A D
authors: AD
authors: Børglum
authors: D
authors: D
authors: Rujescu
authors: H
authors: H
authors: Walter
authors: A
authors: A
authors: Meyer-Lindenberg
authors: N M
authors: NM
authors: Nöthen
authors: R A
authors: RA
authors: Ophoff
authors: S
authors: S
authors: Cichon
mesh_terms: D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005060:Europe; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D006179:Gyrus Cinguli / Q000502:physiology; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance / Q000502:physiology*; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D044465:White People / Q000235:genetics*