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
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: firstname.lastname@example.org
Received April 7, 2010
Accepted November 15, 2010