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

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, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Bonetto, Chiara, Suvisaari, Jaana, Thygesen, Johan Hilge, Pétursson, Hannes, Lönnqvist, Jouko, Sigurdsson, Engilbert, Giegling, Ina, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, 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. and Werge, Thomas 2011. At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia. Biological Psychiatry 70 (1) , pp. 59-63. 10.1016/j.biopsych.2011.01.031

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	diabetes type II, genetic risk variants, rs7903146, schizophrenia, TCF7L2
Publisher:	Elsevier
ISSN:	0006-3223
Last Modified:	19 Oct 2022 10:19
URI:	https://orca.cardiff.ac.uk/id/eprint/23993

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