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

作者：Hansen Thomas^*; Ingason Andres; 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; Petursson Hannes; Lonnqvist Jouko; Sigurdsson Engilbert; Giegling Ina; Craddock Nick; O'Donovan Michael C; Ruggeri Mirella; Cichon Sven; Ophoff Roel A; Pietilainen Olli; Peltonen Leena; Noethen Markus M; Rujescu Dan

来源：Biological Psychiatry, 2011, 70(1): 59-63.

DOI：10.1016/j.biopsych.2011.01.031

• Diabetes type II
• genetic risk variants
• rs7903146
• schizophrenia
• TCF7L2

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.

• 出版日期2011-7-1
• 单位河北医科大学; 上海市精神卫生中心