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 Craddock & 12 others Michael 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

Fingerprint

Type 2 Diabetes Mellitus
Schizophrenia
Comorbidity
Antipsychotic Agents
Life Style
Healthy Volunteers
Alleles
Odds Ratio
Parturition
Confidence Intervals

Keywords

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

Cite this

Hansen, T., Ingason, A., Djurovic, S., Melle, I., Fenger, M., Gustafsson, O., ... 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

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, 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.

In: Biological Psychiatry, Vol. 70, No. 1, 01.07.2011, p. 59-63.

Research output: Contribution to journalArticle

Hansen, T, Ingason, A, Djurovic, S, Melle, I, Fenger, M, Gustafsson, O, Jakobsen, KD, Rasmussen, HB, Tosato, S, Rietschel, M, Frank, J, Owen, M, Bonetto, C, Suvisaari, J, Thygesen, JH, Pétursson, H, Lönnqvist, J, Sigurdsson, E, Giegling, I, Craddock, N, O'Donovan, MC, Ruggeri, M, Cichon, S, Ophoff, RA, Pietiläinen, O, Peltonen, L, Nöthen, MM, Rujescu, D, St Clair, D, Collier, DA, Andreassen, OA & Werge, T 2011, 'At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia' Biological Psychiatry, vol. 70, no. 1, pp. 59-63. https://doi.org/10.1016/j.biopsych.2011.01.031
Hansen T, Ingason A, Djurovic S, Melle I, Fenger M, Gustafsson O et al. At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia. Biological Psychiatry. 2011 Jul 1;70(1):59-63. https://doi.org/10.1016/j.biopsych.2011.01.031
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. / At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia. In: Biological Psychiatry. 2011 ; Vol. 70, No. 1. pp. 59-63.
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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.",
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T1 - At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia

AU - Hansen, Thomas

AU - Ingason, Andrés

AU - Djurovic, Srdjan

AU - Melle, Ingrid

AU - Fenger, Mogens

AU - Gustafsson, Omar

AU - Jakobsen, Klaus D

AU - Rasmussen, Henrik B

AU - Tosato, Sarah

AU - Rietschel, Marcella

AU - Frank, Josef

AU - Owen, Mike

AU - Bonetto, Chiara

AU - Suvisaari, Jaana

AU - Thygesen, Johan Hilge

AU - Pétursson, Hannes

AU - Lönnqvist, Jouko

AU - Sigurdsson, Engilbert

AU - Giegling, Ina

AU - Craddock, Nick

AU - O'Donovan, Michael C

AU - Ruggeri, Mirella

AU - Cichon, Sven

AU - Ophoff, Roel A

AU - Pietiläinen, Olli

AU - Peltonen, Leena

AU - Nöthen, Markus M

AU - Rujescu, Dan

AU - St Clair, David

AU - Collier, David A

AU - Andreassen, Ole A

AU - Werge, Thomas

N1 - Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

KW - diabetes type II

KW - genetic risk variants

KW - rs7903146

KW - TCF7L2

U2 - 10.1016/j.biopsych.2011.01.031

DO - 10.1016/j.biopsych.2011.01.031

M3 - Article

VL - 70

SP - 59

EP - 63

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 1

ER -