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Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.
Mol. Psychiatry 17, 906-917 (2012)
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 x 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. Molecular Psychiatry (2012) 17, 906-917; doi: 10.1038/mp.2011.80; published online 12 July 2011
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Common Variation ; Genome-wide Association Study ; Gwas ; Imaging Genetics ; Schizophrenia; Genome-Wide Association; Bipolar-Disorder; Neural Mechanisms; Common Variants; Disease; System; Risk; Autophagy; Identification; Metaanalysis
Language
Publication Year
2012
HGF-reported in Year
2012
ISSN (print) / ISBN
1359-4184
e-ISSN
1476-5578
Journal
Molecular Psychiatry
Quellenangaben
Volume: 17,
Issue: 9,
Pages: 906-917
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)
POF-Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504100-001
G-503900-002
G-503900-002
WOS ID
WOS:000308063900007
Scopus ID
84866427260
PubMed ID
21747397
Erfassungsdatum
2012-09-27