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; 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

doi:10.1016/j.biopsych.2011.01.031

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

99 Citations (Scopus)

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 language	English
Journal	Biological Psychiatry
Volume	70
Issue number	1
Pages (from-to)	59-63
Number of pages	5
ISSN	0006-3223
DOIs	https://doi.org/10.1016/j.biopsych.2011.01.031
Publication status	Published - 1 Jul 2011

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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

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

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title = "At-Risk Variant in TCF7L2 for Type II Diabetes Increases Risk of Schizophrenia",

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.",

author = "Thomas Hansen and Andr{\'e}s Ingason and Srdjan Djurovic and Ingrid Melle and Mogens Fenger and Omar Gustafsson and Jakobsen, {Klaus D} and Rasmussen, {Henrik B} and Sarah Tosato and Marcella Rietschel and Josef Frank and Mike Owen and Chiara Bonetto and Jaana Suvisaari and Thygesen, {Johan Hilge} and Hannes P{\'e}tursson and Jouko L{\"o}nnqvist and Engilbert Sigurdsson and Ina Giegling and Nick Craddock and O'Donovan, {Michael C} and Mirella Ruggeri and Sven Cichon and Ophoff, {Roel A} and Olli Pietil{\"a}inen and Leena Peltonen and N{\"o}then, {Markus M} and Dan Rujescu and {St Clair}, David and Collier, {David A} and Andreassen, {Ole A} and Thomas Werge",

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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

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.

U2 - 10.1016/j.biopsych.2011.01.031

DO - 10.1016/j.biopsych.2011.01.031

M3 - Journal article

C2 - 21414605

SN - 0006-3223

VL - 70

SP - 59

EP - 63

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 1

ER -

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

Abstract

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