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

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• 作者：Thomas Hansen^a ; ^b ; ^{Thomas.hansen@regionh.dk"" rel=""nofollow} ; Andr&#xe9 ; s Ingason^a ; Srdjan Djurovic^c ; Ingrid Melle^c ; ^d ; Mogens Fenger^e ; Omar Gustafsson^f ; Klaus D. Jakobsen^a ; ^b ; ^g ; Henrik B. Rasmussen^a ; Sarah Tosato^h ; Marcella Rietschel^h ; ⁱ ; Josef Frankⁱ ; Mike Owen^j ; Chiara Bonetto^h ; Jaana Suvisaari^k ; ^l ; ^m ; Johan Hilge Thygesen^a ; Hannes P&#xe9 ; turssonⁿ ; Jouko Lö ; nnqvist^k ; ^l ; ^m ; Engilbert Sigurdssonⁿ ; Ina Giegling^o ; Nick Craddock^j ; Michael C. O'Donovan^j ; Mirella Ruggeri^h ; ⁱ ; Sven Cichon^p ; Roel A. Ophoff^q ; ^r ; Olli Pietil&#xe4 ; inen^k ; ^l ; ^m ; Leena Peltonen^k ; ^l ; ^m ; ^s ; ^t ; Markus M. Nö ; then^u ; Dan Rujescu^o ; David St. Clair^v ; David A. Collier^w ; Ole A. Andreassen^d ; ^f ; Thomas Werge^a
• 关键词：Diabetes type II ; genetic risk variants ; rs7903146 ; schizophrenia ; TCF7L2
• 刊名：Biological Psychiatry
• 出版年：2011
• 出版时间：1 July 2011
• 年：2011
• 卷：70
• 期：1
• 页码：59-63
• 全文大小：347 K

文摘

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.