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

被引：108

作者：

Hansen, Thomas ^{[1
,2
]}

Ingason, Andres ^{[1
]}

Djurovic, Srdjan ^{[3
]}

Melle, Ingrid ^{[3
,4
]}

Fenger, Mogens ^{[5
]}

Gustafsson, Omar ^{[6
]}

Jakobsen, Klaus D. ^{[1
,2
,7
]}

Rasmussen, Henrik B. ^{[1
]}

Tosato, Sarah ^{[8
]}

Rietschel, Marcella ^{[9
]}

Frank, Josef ^{[9
]}

Owen, Mike ^{[10
]}

Bonetto, Chiara ^{[8
]}

Suvisaari, Jaana ^{[11
,12
,13
]}

Thygesen, Johan Hilge ^{[1
]}

Petursson, Hannes ^{[14
]}

Lonnqvist, Jouko ^{[11
,12
,13
]}

Sigurdsson, Engilbert ^{[14
]}

Giegling, Ina ^{[15
]}

Craddock, Nick ^{[10
]}

O'Donovan, Michael C. ^{[10
]}

Ruggeri, Mirella ^{[8
]}

Cichon, Sven ^{[16
,17
]}

Ophoff, Roel A. ^{[18
,19
,20
]}

Pietilainen, Olli ^{[11
,12
,13
]}

Peltonen, Leena ^{[11
,12
,13
,21
,22
,23
]}

Noethen, Markus M. ^{[24
]}

Rujescu, Dan ^{[15
]}

St Clair, David ^{[25
]}

Collier, David A. ^{[26
]}

Andreassen, Ole A. ^{[4
,6
]}

Werge, Thomas ^{[1
]}

机构：

[1] Copenhagen Univ Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, Boserupvej 4, DK-4000 Roskilde, Denmark

[2] Univ Copenhagen, Ctr Pharmacogenom, Copenhagen, Denmark

[3] Univ Oslo, Oslo Univ Hosp Ulleval, Dept Med Genet, Oslo, Norway

[4] Univ Oslo, Inst Psychiat, TOP Project, Oslo, Norway

[5] Copenhagen Univ Hosp, Dept Clin Biochem, Hvidovre, Denmark

[6] Oslo Univ Hosp Ulleval, Dept Psychiat, Oslo, Norway

[7] Copenhagen Univ Hosp, Psychiat Ctr Hvidovre, Hvidovre, Denmark

[8] Univ Verona, Sect Psychiat & Clin Psychol, Dept Publ Hlth & Community Med, I-37100 Verona, Italy

[9] Univ Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany

[10] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales

[11] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[12] Univ Helsinki, Natl Inst Hlth & Welf, Helsinki, Finland

[13] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[14] Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland

[15] Univ Munich, Div Mol & Clin Neurol, Munich, Germany

[16] Forschungszentrum Julich, Inst Neurosci & Med, D-52425 Julich, Germany

[17] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany

[18] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands

[19] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands

[20] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA USA

[21] Wellcome Trust Sanger Inst, Cambridge, England

[22] Harvard Univ, Broad Inst, Boston, MA 02115 USA

[23] MIT, Boston, MA USA

[24] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany

[25] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland

[26] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychol Ctr, London WC2R 2LS, England

来源：

BIOLOGICAL PSYCHIATRY | 2011年 / 70卷 / 01期

基金：

英国医学研究理事会;

关键词：

Diabetes type II; genetic risk variants; rs7903146; schizophrenia; TCF7L2; GENOME-WIDE ASSOCIATION; DRUG-NAIVE PATIENTS; GLUCOSE-TOLERANCE; DEMENTIA-PRAECOX; BLOOD-SUGAR; GENE; LOCI; MELLITUS; INSULIN; IMMUNOREACTIVITY;

D O I：

10.1016/j.biopsych.2011.01.031

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：59 / 63

页数：5

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