C Dubertret1, N Hanoun, J Adès, M Hamon, P Gorwood. 1. Service de Psychiatrie Adulte, Faculty of Bichat-Claude Bernard, Louis Mourier Hospital, Colombes Cedex, France.
Abstract
BACKGROUND: Pharmacological and neurodevelopmental data support the idea that the gene, which codes for the 5-HT(5A) receptor is an important candidate gene for schizophrenia susceptibility. However, previous genetic studies focusing on this gene yielded conflicting results, potentially because of: (i) stratification biases of case-control association studies, (ii) genetic and phenotypic heterogeneity of schizophrenia, and (iii) variability in the loci analyzed (the 5-HT(5A) gene having many polymorphic sites). METHODS: A transmission disequilibrium test was used in the present study aimed at investigating two polymorphisms in exon 1 of the 5-HT(5A) gene, the A12T silent substitution and the C43T transversion leading to a 15Pro --> Ser substitution, in 103 patients with DSM-IV diagnosis of schizophrenia, and their 206 parents. RESULTS: We found an excess of transmission of the 12T allele from the parents to their affected children (P = 0.02), with evidence for linkage disequilibrium between the 12T-43C haplotype and schizophrenia (P = 0.002). Furthermore, patients with the 12T allele had a significantly later age at onset (P = 0.003), and the Q-TDT approach confirmed that this allele was transmitted with an older age at onset (P = 0.01). CONCLUSIONS: These data provided convergent evidence for a significant role of the 5-HT(5A) gene in schizophrenia and more specifically in patients with later age at onset.
BACKGROUND: Pharmacological and neurodevelopmental data support the idea that the gene, which codes for the 5-HT(5A) receptor is an important candidate gene for schizophrenia susceptibility. However, previous genetic studies focusing on this gene yielded conflicting results, potentially because of: (i) stratification biases of case-control association studies, (ii) genetic and phenotypic heterogeneity of schizophrenia, and (iii) variability in the loci analyzed (the 5-HT(5A) gene having many polymorphic sites). METHODS: A transmission disequilibrium test was used in the present study aimed at investigating two polymorphisms in exon 1 of the 5-HT(5A) gene, the A12T silent substitution and the C43T transversion leading to a 15Pro --> Ser substitution, in 103 patients with DSM-IV diagnosis of schizophrenia, and their 206 parents. RESULTS: We found an excess of transmission of the 12T allele from the parents to their affected children (P = 0.02), with evidence for linkage disequilibrium between the 12T-43C haplotype and schizophrenia (P = 0.002). Furthermore, patients with the 12T allele had a significantly later age at onset (P = 0.003), and the Q-TDT approach confirmed that this allele was transmitted with an older age at onset (P = 0.01). CONCLUSIONS: These data provided convergent evidence for a significant role of the 5-HT(5A) gene in schizophrenia and more specifically in patients with later age at onset.
Authors: Y Zhang; E M Smith; T M Baye; J V Eckert; L J Abraham; E K Moses; A H Kissebah; L J Martin; M Olivier Journal: Physiol Genomics Date: 2010-04-13 Impact factor: 3.107
Authors: Ricky S Joshi; Paras Garg; Noah Zaitlen; Tuuli Lappalainen; Corey T Watson; Nidha Azam; Daniel Ho; Xin Li; Stylianos E Antonarakis; Han G Brunner; Karin Buiting; Sau Wai Cheung; Bradford Coffee; Thomas Eggermann; David Francis; Joep P Geraedts; Giorgio Gimelli; Samuel G Jacobson; Cedric Le Caignec; Nicole de Leeuw; Thomas Liehr; Deborah J Mackay; Stephen B Montgomery; Alistair T Pagnamenta; Peter Papenhausen; David O Robinson; Claudia Ruivenkamp; Charles Schwartz; Bernhard Steiner; David A Stevenson; Urvashi Surti; Thomas Wassink; Andrew J Sharp Journal: Am J Hum Genet Date: 2016-08-25 Impact factor: 11.025