At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia

Thomas Hansen, Andrés Ingason, Srdjan Djurovic, Ingrid Melle, Mogens Fenger, Omar Gustafsson, Klaus D Jakobsen, Henrik B Rasmussen, Sarah Tosato, Marcella Rietschel, Josef Frank, Mike Owen, Chiara Bonetto, Jaana Suvisaari, Johan Hilge Thygesen, Hannes Pétursson, Jouko Lönnqvist, Engilbert Sigurdsson, Ina Giegling, Nick CraddockMichael C O'Donovan, Mirella Ruggeri, Sven Cichon, Roel A Ophoff, Olli Pietiläinen, Leena Peltonen, Markus M Nöthen, Dan Rujescu, David St Clair, David A Collier, Ole A Andreassen, Thomas Werge

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)59-63
Number of pages5
JournalBiological Psychiatry
Volume70
Issue number1
DOIs
Publication statusPublished - 1 Jul 2011

Keywords

  • diabetes type II
  • genetic risk variants
  • rs7903146
  • TCF7L2

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    Hansen, T., Ingason, A., Djurovic, S., Melle, I., Fenger, M., Gustafsson, O., Jakobsen, K. D., Rasmussen, H. B., Tosato, S., Rietschel, M., Frank, J., Owen, M., Bonetto, C., Suvisaari, J., Thygesen, J. H., Pétursson, H., Lönnqvist, J., Sigurdsson, E., Giegling, I., ... Werge, T. (2011). At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia. Biological Psychiatry, 70(1), 59-63. https://doi.org/10.1016/j.biopsych.2011.01.031