Family-based association studies between 5-HT5A receptor gene and schizophrenia.
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.
Dubertret
C
C
Service de Psychiatrie Adulte, Faculty of Bichat-Claude Bernard, Louis Mourier Hospital, Colombes Cedex, France.
Hanoun
N
N
Adès
J
J
Hamon
M
M
Gorwood
P
P
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D011985:Receptors, Serotonin; C078730:serotonin 5 receptor