Rs25531

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." Looking at OpenSNP frequency data, this seems to be universal for direct to consumer genotyping services at this stage.

The minor allele (G) of rs25531 is almost always in phase with the long (L) allele of the 5-HTTLPR, which is the most commonly studied variation in this region. The (L) long allele may be associated with lower levels of serotonin.

The article and video from "The Atlantic" suggests that children with the short allele (A), may need and benefit greatly from more maternal support
 * http://www.theatlantic.com/doc/200912/dobbs-orchid-gene

In contrast to earlier reports linking rs25531, a SNP in the serotonin transporter SLC6A4 gene, to obsessive compulsive disorder (OCD), a March 2007 publication finds no significant association studying "the largest sample size of OCD patients (N=347) and controls (N=749) ever investigated".

A separate study of 75 patients suffering mood disorders after traumatic brain injury (TBI) concluded that there was no evidence of association between rs25531 and depression post-TBI.

A small study (62 patients and 62 matched controls) investigated this SNP in relation to blushing. (Blushing is considered to be one of the prime pathophysiological markers of social anxiety disorder.) The less active 5-HTTLPR genotypes were nominally significantly associated with increased blushing propensity in patients with social anxiety disorder, and association remained significant even when statistically controlled for he influence of depression.

A study of 94 depressed patients who attempted suicide compared to 94 without psychiatric disorders found no evidence of an association with rs25531.

A study of 97 "normal" individuals concluded that rs25531(G;G) individuals selectively process positive affective material alongside selective avoidance of negative affective material, in a manner absent among individuals carrying a rs25531(A) allele. To put it another way, if this conclusion drawn from a very small sample of people can be replicated, rs25531(G;G) individuals may have a tendency to be optimists and to be more resilient to stress.

A study published in 2011 of 2,500+ individuals followed from 1995 - 2008 as part of the US National Longitudinal Study of Adolescent Health found that twice as many respondents with two 5-HTTLPR long variants said they were very satisfied with life compared with carriers of two short versions. Conversely, 26% of those carrying two short alleles said they were dissatisfied with life, compared with 20% of people carrying two long variants. This blog post investigates the statistics.

A study of 135 patients with major depressive disorder (mean age 31.1+/-11.6 years, 68% females) treated with escitalopram 10-20 mg/day for 12 weeks concluded that patients carrying the rs25531(A) allele may be at increased risk for side effects (e.g. headaches), but they say no associations with efficacy.

Protocol for genotyping rs25531