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Family-based association studies between 5-HT5A receptor gene and schizophrenia
C Dubertret1, N Hanoun, J Adès
1Service de Psychiatrie Adulte, Faculty of Bichat-Claude Bernard, Louis Mourier Hospital, Colombes Cedex, France.
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.
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