TY  - JOUR
AU  - Hansen, T.
AU  - Ingason, A.
AU  - Djurovic, S.
AU  - Melle, I.
AU  - Fenger, M.
AU  - Gustafsson, O.
AU  - Jakobsen, K.D.
AU  - Ramussen, H.B.
AU  - Tosato, S.
AU  - Rietschel, M.
AU  - Frank, J.
AU  - Owen, M.
AU  - Bonetto, C.
AU  - Suvisaari, J.
AU  - Thygesen, J.H.
AU  - Petursson, H.
AU  - Lönnqvist, J.
AU  - Sigurdsson, E.
AU  - Giegling, I.
AU  - Craddock, N.
AU  - O'Donovan, M.C.
AU  - Ruggeri, M.
AU  - Cichon, S.
AU  - Ophoff, R.A.
AU  - Pietiläinen, O.
AU  - Peltonen, L.
AU  - Nöthen, M.M.
AU  - Rujescu, D.
AU  - St. Clair, D.
AU  - Collier, D.A.
AU  - Andreassen, O.A.
AU  - Werge, T.
TI  - At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia
JO  - Biological psychiatry
VL  - 70
SN  - 0006-3223
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - PreJuSER-17372
SP  - 59 - 63
PY  - 2011
N1  - We thank Hreinn Stefansson (DeCODE Genetics) for making the Icelandic data available and commenting the manuscript. Sadly, Leena Peltonen passed away after this study was ended. We acknowledge the expert assistance of numerous mental health professionals in the various clinical departments. This work was sponsored by European Union grants LSHM-CT-2006-037761 (Project SGENE, http://www.sgene.eu) and PIAP-GA-2008-218251 (Project PsychGene, http://www.psych-gene.eu). The work was also supported by grants to Thomas Werge from the Copenhagen Hospital Corporation Research Fund and the Danish National Psychiatric Research Foundation, the Danish Agency for Science, Technology and Innovation (Centre for Pharmacogenomics), and the Danish Medical Research Council. The Research Council of Norway supported the study (Grant Nos. 167153/v50 and 163070/V50) together with Norwegian South-Eastern Health Authority (Grant No. 123-2004) and University of Oslo and Oslo University Hospital. Eli Lilly, Inc., funded parts of the genotyping of the Norwegian sample.
AB  - Schizophrenia is associated with increased risk of type II diabetes and metabolic disorders. However, it is unclear whether this comorbidity reflects shared genetic risk factors, at-risk lifestyle, or side effects of antipsychotic medication.Eleven known risk variants of type II diabetes were genotyped in patients with schizophrenia in a sample of 410 Danish patients, each matched with two healthy control subjects on sex, birth year, and month. Replication was carried out in a large multinational European sample of 4089 patients with schizophrenia and 17,597 controls (SGENE+) using Mantel-Haenszel test.One type II diabetes at-risk allele located in TCF7L2, rs7903146 [T], was associated with schizophrenia in the discovery sample (p = .0052) and in the replication with an odds ratio of 1.07 (95% confidence interval 1.01-1.14, p = .033).The association reported here with a well-known diabetes variant suggests that the observed comorbidity is partially caused by genetic risk variants. This study also demonstrates how genetic studies can successfully examine an epidemiologically derived hypothesis of comorbidity.
KW  - Alleles
KW  - Case-Control Studies
KW  - Diabetes Mellitus, Type 2: genetics
KW  - Female
KW  - Genetic Association Studies: methods
KW  - Genetic Predisposition to Disease: genetics
KW  - Genotype
KW  - Humans
KW  - Male
KW  - Polymorphism, Single Nucleotide
KW  - Schizophrenia: genetics
KW  - Transcription Factor 7-Like 2 Protein: genetics
KW  - TCF7L2 protein, human (NLM Chemicals)
KW  - Transcription Factor 7-Like 2 Protein (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21414605
UR  - <Go to ISI:>//WOS:000291559300012
DO  - DOI:10.1016/j.biopsych.2011.01.031
UR  - https://juser.fz-juelich.de/record/17372
ER  -