Predicting anxiety-related personality traits by means of serotonergic VNTR variants STin2 and 5-HTTLPR

Polymorphisms of the serotonergic system are amongst the most commonly investigated genetic variants with respect to anxiety-related personality traits and affective disorders. Mostly the prominent 5-HTTLPR, a functional VNTR in the 5-HTT promoter region, is intensively analysed but effect sizes in meta-analyses are small and results are inconsistent. We reinvestigated the association of 5-HTTLPR with harm avoidance (HA) and neuroticism taking another functional 5-HTT-VNTR (STin2) into account, as both VNTRs have transcription regulating properties and research points to combinatorial effects on transcription efficacy. N = 2969 participants, among them 447 inpatients suffering from affective disorders, were genotyped and filled in the TCI, NEO-FFI personality inventories besides the CLEq measuring the extent of experienced stressful life events. Significant main effects for the 5-HTTLPR with inpatients carrying the L+ allele having lower HA scores as well as for the STin2 with healthy controls carrying at least one STin2.12R allele having lower neuroticism scores were observed. Besides no gene-interaction occurred. However, specific haplotype effects were observed in healthy participants as well as in the total sample. More specifically, the 12/L variant was associated with significant lower HA and neuroticism scores. Results highlight the multifactorial interplay of 5-HTT genetic variants and the use of haplotypes in association studies on anxiety-related personality traits with impact on affective disorders.