Genetic variation in the serotonin 2A receptor and suicidal Ideation in a sample of 270 irish high-density schizophrenia families

Genetic variation in the serotonin 2A receptor (HTR2A) has been associated with both schizophrenia and suicidal behavior. Our sample comprised 270 Irish high-density schizophrenia families (n = 1,408 subjects, including 755 with psychotic illness). Diagnoses were generated using a modified SCID. All patients who had at least one episode of psychosis were rated on the Operation Criteria Checklist for Psychotic Illness (OPCRIT). Lifetime history of suicidal ideation was determined from medical records and psychiatric interviews and was scored in the OPCRIT. Twelve SNPs were selected for study. Ten of these were tagSNPs derived from HapMap data, along with His452Tyr and T102C. We tested for association with psychotic illness as a whole, as well as stratified by the presence of suicidal ideation, using FBAT and PDTPHASE. Single-marker as well as haplotype-based tests using a ''sliding window'' approach were performed. We observed several 2,3, and 4 marker haplotypes near the 3' end of the gene that were over-transmitted to psychotic subjects (0.02 ≤ P ≤ 0.04). His452Tyr was included in these haplotypes but was not itself significant. We also observed modest over-transmission of a 2-marker haplotype that included T102C (0.04 ≤ P≤ 0.08), which was also not itself significant in single-marker analyses. There was no significant association in the subgroup of the sample with suicidal ideation. Because of multiple testing, these results do not provide support for HTR2A as a susceptibility gene for psychotic illness, or for suicidal ideation within psychotic illness.