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5-HTTLPR

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5-HTTLPR (serotonin-transporter-linked polymorphic region) is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter. It has been extensively investigated in connection with the behavioral, psychiatric, pharmacogenetic aspects of neuropsychiatric disorders.

In contrast to earlier reports, a June 2009 article in JAMA showed no association between 5-HTTLPR genotype and depression.

geneticfuture discusses an article; [PMID 19052197] about the genetics of the placebo effect, which associates placebo response with homozygosity of the 5-HTTLPR long allele (and also rs4570625).

blog the effectiveness of placebo treatment for social anxiety disorder may be influenced by this

Genotyping[edit]

While many subtypes exist it can be partially genotyped based on rs25531 and rs25532; the minor allele (G) of rs25531 is almost always in phase with the long (L) allele of 5-HTTLPR.[PMID 18055562]

According to David Hinds of 23andMe on community forums, "nearly everyone (99.97%) is getting called as CC, and there is no clear heterozygote cluster" ... "the genotype calls for rs25531 on our platform are not meaningful." Based on [PMID 16402131] people with one or two short-form alleles may be getting no-call for rs25531; as supporting evidence the OpenSNP no-call rate matches expected European rate of short alleles. This is a 23andMe custom SNP on the microarray, so exact binding sequence isn't public knowledge.

Based on [PMID 21670732] with 2823 samples a haplotype of A+A in rs2129785+rs11867581 predicts short allele with good accuracy. Haplotype G+G has not been generally observed, so phase can always be determined. The only possible haplotypes are thus A+A short 91% of the time, A+G long 96% of the time and G+A always long. Another study [PMID 22504458] uses regression model over eight SNP's available on Illumina microarray with higher expected accuracy.