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The tryptophan hydroxylase 1 ( TPH1 ) gene, schizophrenia susceptibility, and suicidal behavior: A multi‐centre case–control study and meta‐analysis
Author(s) -
Saetre Peter,
Lundmark Per,
Wang August,
Hansen Thomas,
Rasmussen Henrik B.,
Djurovic Srdjan,
Melle Ingrid,
Andreassen Ole A.,
Werge Thomas,
Agartz Ingrid,
Hall Håkan,
Terenius Lars,
Jönsson Erik G.
Publication year - 2010
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30991
Subject(s) - single nucleotide polymorphism , tryptophan hydroxylase , locus (genetics) , genetics , allele , odds ratio , psychiatry , medicine , genotype , biology , gene , serotonin , serotonergic , receptor
Serotonin (5‐hydroxytryptamin; 5‐HT) alternations has since long been suspected in the pathophysiology of schizophrenia. Tryptophan hydroxylase (tryptophan 5‐monooxygenase; TPH) is the rate‐limiting enzyme in the biosynthesis of 5‐HT, and sequence variation in intron 6 of the TPH1 gene has been associated with schizophrenia. The minor allele (A) of this polymorphism (A218C) is also more frequent in patients who have attempted suicide and individuals who died by suicide, than in healthy control individuals. In an attempt to replicate previous findings, five single nucleotide polymorphisms (SNPs) were genotyped in 837 Scandinavian schizophrenia patients and 1,473 controls. Three SNPs spanning intron 6 and 7, including the A218C and A779C polymorphisms, were associated with schizophrenia susceptibility ( P = 0.019). However there were no differences in allele frequencies of these loci between affected individuals having attempted suicide at least once and patients with no history of suicide attempts ( P = 0.84). A systematic literature review and meta‐analysis support the A218C polymorphism as a susceptibility locus for schizophrenia (odds ratio 1.17, 95% confidence interval 1.07–1.29). Association studies on suicide attempts are however conflicting (heterogeneity index I 2 = 0.54) and do not support the A218C/A779C polymorphisms being a susceptibility locus for suicidal behavior among individuals diagnosed with a psychiatric disorder (OR = 0.96 [0.80–1.16]). We conclude that the TPH1 A218/A779 locus increases the susceptibility of schizophrenia in Caucasian and Asian populations. In addition, the data at hand suggest that the locus contributes to the liability of psychiatric disorders characterized by elevated suicidal rates, rather than affecting suicidal behavior of individuals suffering from a psychiatric disorder. © 2009 Wiley‐Liss, Inc.