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Dual association of a TRKA polymorphism with schizophrenia

Van Schijndel, Jessica E.a; Van Zweeden, Martinea; Van Loo, Karen M.J.a; Djurovic, Srdjanb; Andreassen, Ole A.b,c,d; Hansen, Thomase; Werge, Thomase; Nyegaard, Mettef,k,h; Sørensen, Karina Medenj; Nordentoft, Meretek; Mortensen, Preben B.g; Mors, Olei; Børglum, Anders D.f,i; Del-Favero, Jurgenm,n; Norrback, Karl-Fredrikn,q,r; Adolfsson, Rolfq,r; Hert, Marc Deo; Claes, Stephanp; Cichon, Svens,t,u; Rietschel, Marcellav; Nöthen, Markus M.s,u; Kallunki, Pekkal; Pedersen, Jan T.l; Martens, Gerard J.M.a

doi: 10.1097/YPG.0b013e3283437194
Original Articles

Objective An interaction between predisposing genes and environmental stressors is thought to underlie the neurodevelopmental disorder schizophrenia. In a targeted gene screening, we previously found that the minor allele of the single nucleotide polymorphism (SNP) rs6336 in the neurotrophic tyrosine kinase receptor 1 (NTRK1/TRKA) gene is associated with schizophrenia as a risk factor.

Methods We genotyped the TRKA SNP in a total of eight independent Caucasian schizophrenia case–control groups.

Result Remarkably, although in five of the groups a higher frequency of the risk allele was indeed found in the patients compared with the controls, in the three other groups the SNP acted as a protective factor.

Conclusion An intriguing possibility is that this dual character of the TRKA SNP is caused by its interaction with endophenotypic and/or epistatic factors.

aDepartment of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience and Nijmegen Centre for Molecular Life Sciences (NCMLS), Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands

bInstitute of Psychiatry, University of Oslo

cDepartments of Medical Genetics

dPsychiatry, Oslo University Hospital – Ulleval, Oslo, Norway

eResearch Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde

fDepartment of Human Genetics

gNational Centre for Register-based Research, Aarhus University, Aarhus C

hDepartment of Haematology, Aarhus University Hospital, Aalborg Hospital, Aalborg

iCentre for Psychiatric Research, Aarhus University Hospital, Risskov

jMolecular Genetics Laboratory, Department of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen S

kPsychiatric Centre Bispebjerg, Copenhagen University, Bispebjerg Bakke, Copenhagen NV

lH. Lundbeck A/S, DK-2500 Valby, Copenhagen, Denmark

mApplied Molecular Genomics Group, VIB Department of Molecular Genetics

nUniversity of Antwerp, Antwerp

oCampus Kortenberg

pCampus Leuven, University Psychiatric Centre, Catholic University Louvain, Belgium

qDepartment of Clinical Sciences, Psychiatry, Umeå University, Umeå

rDepartment of Psychiatry, Hospital of Sunderby, Luleå, Sweden

sInstitute of Human Genetics

tDepartment of Genomics, Life and Brain Center, University of Bonn, Bonn

uInstitute of Neurosciences and Medicine (INM-1), Research Center Juelich, Juelich

vDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany

Correspondence to Gerard J.M. Martens, PhD, Donders Institute for Brain, Cognition and Behaviour and Nijmegen Centre for Molecular Life Sciences, NCMLS RT282, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands Tel: +31 24 3610564; fax: +31 24 3615317; e-mail:

Received April 7, 2010

Accepted November 15, 2010

© 2011 Lippincott Williams & Wilkins, Inc.