PMID- 18668039
OWN - NLM
STAT- MEDLINE
DCOM- 20081021
LR  - 20250529
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 455
IP  - 7210
DP  - 2008 Sep 11
TI  - Large recurrent microdeletions associated with schizophrenia.
PG  - 232-6
LID - 10.1038/nature07229 [doi]
AB  - Reduced fecundity, associated with severe mental disorders, places negative 
      selection pressure on risk alleles and may explain, in part, why common variants 
      have not been found that confer risk of disorders such as autism, schizophrenia 
      and mental retardation. Thus, rare variants may account for a larger fraction of 
      the overall genetic risk than previously assumed. In contrast to rare single 
      nucleotide mutations, rare copy number variations (CNVs) can be detected using 
      genome-wide single nucleotide polymorphism arrays. This has led to the 
      identification of CNVs associated with mental retardation and autism. In a 
      genome-wide search for CNVs associating with schizophrenia, we used a 
      population-based sample to identify de novo CNVs by analysing 9,878 transmissions 
      from parents to offspring. The 66 de novo CNVs identified were tested for 
      association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three 
      deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with 
      schizophrenia in the first sample (phase I) were followed up in a second sample 
      of 3,285 cases and 7,951 controls (phase II). All three deletions significantly 
      associate with schizophrenia and related psychoses in the combined sample. The 
      identification of these rare, recurrent risk variants, having occurred 
      independently in multiple founders and being subject to negative selection, is 
      important in itself. CNV analysis may also point the way to the identification of 
      additional and more prevalent risk variants in genes and pathways involved in 
      schizophrenia.
FAU - Stefansson, Hreinn
AU  - Stefansson H
AD  - CNS Division, deCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
FAU - Rujescu, Dan
AU  - Rujescu D
FAU - Cichon, Sven
AU  - Cichon S
FAU - Pietilainen, Olli P H
AU  - Pietilainen OP
FAU - Ingason, Andres
AU  - Ingason A
FAU - Steinberg, Stacy
AU  - Steinberg S
FAU - Fossdal, Ragnheidur
AU  - Fossdal R
FAU - Sigurdsson, Engilbert
AU  - Sigurdsson E
FAU - Sigmundsson, Thordur
AU  - Sigmundsson T
FAU - Buizer-Voskamp, Jacobine E
AU  - Buizer-Voskamp JE
FAU - Hansen, Thomas
AU  - Hansen T
FAU - Jakobsen, Klaus D
AU  - Jakobsen KD
FAU - Muglia, Pierandrea
AU  - Muglia P
FAU - Francks, Clyde
AU  - Francks C
FAU - Matthews, Paul M
AU  - Matthews PM
FAU - Gylfason, Arnaldur
AU  - Gylfason A
FAU - Halldorsson, Bjarni V
AU  - Halldorsson BV
FAU - Gudbjartsson, Daniel
AU  - Gudbjartsson D
FAU - Thorgeirsson, Thorgeir E
AU  - Thorgeirsson TE
FAU - Sigurdsson, Asgeir
AU  - Sigurdsson A
FAU - Jonasdottir, Adalbjorg
AU  - Jonasdottir A
FAU - Jonasdottir, Aslaug
AU  - Jonasdottir A
FAU - Bjornsson, Asgeir
AU  - Bjornsson A
FAU - Mattiasdottir, Sigurborg
AU  - Mattiasdottir S
FAU - Blondal, Thorarinn
AU  - Blondal T
FAU - Haraldsson, Magnus
AU  - Haraldsson M
FAU - Magnusdottir, Brynja B
AU  - Magnusdottir BB
FAU - Giegling, Ina
AU  - Giegling I
FAU - Moller, Hans-Jurgen
AU  - Moller HJ
FAU - Hartmann, Annette
AU  - Hartmann A
FAU - Shianna, Kevin V
AU  - Shianna KV
FAU - Ge, Dongliang
AU  - Ge D
FAU - Need, Anna C
AU  - Need AC
FAU - Crombie, Caroline
AU  - Crombie C
FAU - Fraser, Gillian
AU  - Fraser G
FAU - Walker, Nicholas
AU  - Walker N
FAU - Lonnqvist, Jouko
AU  - Lonnqvist J
FAU - Suvisaari, Jaana
AU  - Suvisaari J
FAU - Tuulio-Henriksson, Annamarie
AU  - Tuulio-Henriksson A
FAU - Paunio, Tiina
AU  - Paunio T
FAU - Toulopoulou, Timi
AU  - Toulopoulou T
FAU - Bramon, Elvira
AU  - Bramon E
FAU - Di Forti, Marta
AU  - Di Forti M
FAU - Murray, Robin
AU  - Murray R
FAU - Ruggeri, Mirella
AU  - Ruggeri M
FAU - Vassos, Evangelos
AU  - Vassos E
FAU - Tosato, Sarah
AU  - Tosato S
FAU - Walshe, Muriel
AU  - Walshe M
FAU - Li, Tao
AU  - Li T
FAU - Vasilescu, Catalina
AU  - Vasilescu C
FAU - Muhleisen, Thomas W
AU  - Muhleisen TW
FAU - Wang, August G
AU  - Wang AG
FAU - Ullum, Henrik
AU  - Ullum H
FAU - Djurovic, Srdjan
AU  - Djurovic S
FAU - Melle, Ingrid
AU  - Melle I
FAU - Olesen, Jes
AU  - Olesen J
FAU - Kiemeney, Lambertus A
AU  - Kiemeney LA
FAU - Franke, Barbara
AU  - Franke B
CN  - GROUP
FAU - Sabatti, Chiara
AU  - Sabatti C
FAU - Freimer, Nelson B
AU  - Freimer NB
FAU - Gulcher, Jeffrey R
AU  - Gulcher JR
FAU - Thorsteinsdottir, Unnur
AU  - Thorsteinsdottir U
FAU - Kong, Augustine
AU  - Kong A
FAU - Andreassen, Ole A
AU  - Andreassen OA
FAU - Ophoff, Roel A
AU  - Ophoff RA
FAU - Georgi, Alexander
AU  - Georgi A
FAU - Rietschel, Marcella
AU  - Rietschel M
FAU - Werge, Thomas
AU  - Werge T
FAU - Petursson, Hannes
AU  - Petursson H
FAU - Goldstein, David B
AU  - Goldstein DB
FAU - Nothen, Markus M
AU  - Nothen MM
FAU - Peltonen, Leena
AU  - Peltonen L
FAU - Collier, David A
AU  - Collier DA
FAU - St Clair, David
AU  - St Clair D
FAU - Stefansson, Kari
AU  - Stefansson K
LA  - eng
GR  - R01MH71425-01A1/MH/NIMH NIH HHS/United States
GR  - R01 MH078075/MH/NIMH NIH HHS/United States
GR  - R01 MH071425/MH/NIMH NIH HHS/United States
GR  - G0901310/MRC_/Medical Research Council/United Kingdom
GR  - 089061/WT_/Wellcome Trust/United Kingdom
GR  - PDA/02/06/016/DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
SB  - IM
CIN - Nature. 2008 Sep 11;455(7210):178-9. doi: 10.1038/455178a. PMID: 18784712
CIN - Nat Rev Genet. 2008 Sep;9(9):654. doi: 10.1038/nrg2437. PMID: 21491642
MH  - China
MH  - Chromosomes, Human, Pair 1/genetics
MH  - Chromosomes, Human, Pair 15/genetics
MH  - Europe
MH  - Gene Dosage/genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome, Human/genetics
MH  - Genotype
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Models, Genetic
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Psychotic Disorders/genetics
MH  - Schizophrenia/*genetics
MH  - Sequence Deletion/*genetics
PMC - PMC2687075
MID - UKMS4373
OID - NLM: UKMS4373
FIR - Kahn, Rene S
IR  - Kahn RS
FIR - Linszen, Don H
IR  - Linszen DH
FIR - van Os, Jim
IR  - van Os J
FIR - Wiersma, Durk
IR  - Wiersma D
FIR - Bruggeman, Richard
IR  - Bruggeman R
FIR - Cahn, Wiepke
IR  - Cahn W
FIR - de Haan, Lieuwe
IR  - de Haan L
FIR - Krabbendam, Lydia
IR  - Krabbendam L
FIR - Myin-Germeys, Inez
IR  - Myin-Germeys I
EDAT- 2008/08/01 09:00
MHDA- 2008/10/22 09:00
PMCR- 2009/05/27
CRDT- 2008/08/01 09:00
PHST- 2008/04/17 00:00 [received]
PHST- 2008/09/11 00:00 [revised]
PHST- 2008/07/08 00:00 [accepted]
PHST- 2008/08/01 09:00 [pubmed]
PHST- 2008/10/22 09:00 [medline]
PHST- 2008/08/01 09:00 [entrez]
PHST- 2009/05/27 00:00 [pmc-release]
AID - nature07229 [pii]
AID - 10.1038/nature07229 [doi]
PST - ppublish
SO  - Nature. 2008 Sep 11;455(7210):232-6. doi: 10.1038/nature07229.