Additional findings over G × E at the serotonin transporter continue to accumulate, developing in two directions. One is the incorporation of additional sequence variants at the locus itself. Following the discovery that a single nucleotide polymorphism within one of the long alleles of the repeat means there is an ‘Lg’ allele with lower transcriptional efficacy (functionally therefore behaving like the ‘short’ allele) researchers now report G × E with additional alleles. However, justification for testing these additional alleles is weak. There has been no systematic investigation of the variants that contribute to expression variation in the transporter gene, but testing the effect of 55 SNPs distributed in a 100 kb window surrounding the serotonin transporter locus, as well as the length polymorphism made two important observations [25]. First, two SNPs in linkage disequilibrium explained 50% of variation in transcript abundance; the 5-HTTLPR contributed only 20%. Second, the Lg allele did not significantly contribute to variation. Thus we still lack comprehensive analysis of the relationship between functional variants at the 5-HTTLPR locus and phenotypic variation.
