Subsequent studies suggest a nuanced relationship between the 5-HTTLPR polymorphism and psychiatric disorders. First, although most studies have considered the 5-HTTLPR polymorphism to be functionally bi-allelic, researchers have identified additional alleles. Gelernter et al. [3] identified two uncommon alleles that are longer than the L variant: 1) an extra-long allele (XL) was found in both an African American and a Japanese sample; and 2) a single instance of an allele of length between the L and XL alleles (VL) was also observed in the Japanese sample. In the same year, Delbruck and colleagues [4] identified a “novel allelic variant” (XL) among persons of African origin but not among Caucasians or East Asians. One study in Japan reported two XL variants–with 18 and 20 repeats [5]–whereas another identified alleles with 19 and 20 repeats in a Japanese sample [6]. With more detailed genotyping of 5-HTTLPR among Japanese and Caucasian subjects, Nakamura et al. [7] identified four S alleles and six L alleles as well a few other variants (15-, 19-, 20- and 22-repeats) found only in the Japanese sample. Thus, a dichotomous classification of 5-HTTLPR is likely to obscure potential differences in allele effects.
