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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)
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DOI
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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
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
13.668
2.517
86
87
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Sprache
Veröffentlichungsjahr
2012
HGF-Berichtsjahr
2012
ISSN (print) / ISBN
1359-4184
e-ISSN
1476-5578
Zeitschrift
Molecular Psychiatry
Quellenangaben
Band: 17,
Heft: 9,
Seiten: 906-917
Verlag
Nature Publishing Group
Begutachtungsstatus
Peer reviewed
Institut(e)
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
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-504100-001
G-503900-002
G-503900-002
WOS ID
WOS:000308063900007
Scopus ID
84866427260
PubMed ID
21747397
Erfassungsdatum
2012-09-27