Linkage and association between serotonin 2A receptor gene polymorphisms and bipolar I disorder

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Abstract
Several inconsistent associations between bipolar I disorder (BD1) and polymorphisms of the genes encoding the serotonin 2A receptor (HTR2A) have been published. We conducted the Transmission Disequilibrium Test (TDT) and case-control comparisons involving nine single nucleotide polymorphisms at the serotonin 2A receptor gene (four SNPs of HTR2A exons and five flanking SNPs). Comparison of BD1 cases (n = 93) with a group of unrelated population based controls (n = 92) revealed associations with SNPs on exons 2 and 3 (516C/T and 1354C/T, respectively), consistent with haplotype-based differences. Analysis of the cases and their available parents using the TDT suggested significant linkage and associations with 1354C/T, as well as haplotypes bearing this SNP. Our results support an etiological role for HTR2A in BD1. In view of the relatively small sample, replicate studies using large samples are needed.