At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia

Background 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. Methods Eleven known risk variants of type II...

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Published in:Biological psychiatry (1969) 2011-07, Vol.70 (1), p.59-63
Main Authors: Hansen, Thomas, Ingason, Andrés, Djurovic, Srdjan, Melle, Ingrid, Fenger, Mogens, Gustafsson, Omar, Jakobsen, Klaus D, Rasmussen, Henrik B, Tosato, Sarah, Rietschel, Marcella, Frank, Josef, Owen, Mike, Bonetto, Chiara, Suvisaari, Jaana, Thygesen, Johan Hilge, Pétursson, Hannes, Lönnqvist, Jouko, Sigurdsson, Engilbert, Giegling, Ina, Craddock, Nick, O'Donovan, Michael C, Ruggeri, Mirella, Cichon, Sven, Ophoff, Roel A, Pietiläinen, Olli, Peltonen, Leena, Nöthen, Markus M, Rujescu, Dan, St. Clair, David, Collier, David A, Andreassen, Ole A, Werge, Thomas
Format: Article
Language:English
Subjects:
Alleles
Case-Control Studies
Diabetes Mellitus, Type 2 - genetics
Diabetes type II
Female
Genetic Association Studies - methods
Genetic Predisposition to Disease - genetics
genetic risk variants
Genotype
Humans
Male
Polymorphism, Single Nucleotide
Psychiatry
rs7903146
schizophrenia
Schizophrenia - genetics
TCF7L2
Transcription Factor 7-Like 2 Protein - genetics
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Summary:Background 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. Methods 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. Results 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). Conclusion 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.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2011.01.031