This is partially at odds with what we had originally proposed, i.e., that P trait was proposed to be associated with LPR SS genotype.
We do agree that VNTR STin2 12/12 genotype seems to be non-P. However, it looks like it is the the long form, rather than the short form, of LPR (LL) that is likely related to P trait.
Thus, I think the hypothesis should have been:
• LPR/short form, and STin2/12 are related to non-P trait
• LPR/long form, and STin2/9 & STin2/10 are related to P trait
Here is our original posting:
Posted by ABenis on July 27, 2011, 9:56 pm
"Rather than DRD4, I think that a better case cane be made for 5-HTT as the locus for trait P.
Taking a cue from trait A- (presumably coded by COMT), the P trait is not a phenotype in itself, but a trait modifier (there is no “P” personality phenotype). Thus, the P gene should appear, like COMT, in many studies as “a lot of smoke but little fire.” As we saw in the case of schizophrenia, an allele corresponding to trait P can appear easily as “risk” or “protective” even though not being involved in the etiology of the condition.
With trait P, the gene should appear loosely in studies of conditions that we associate (at least somewhat) with the P trait. These would be studies of autism, schizophrenia, obsessive-compulsive symptoms (but not necessarily OCD), unipolar and post-partum depression, and studies where the personality trait of “persistence”is measured. Also, in habitancies where the P trait is common, on could add fibromyalgia, anorexia nervosa, shyness, social phobia, elevated “harm avoidance” and panic disorder. Finally, we might have a look at migraine because of the urban legend connecting it perfectionism.
The 5-HT Transporter gene (SERT, SL6A4) is on chromosome 17. Two main markers are usually reported: LPR in the promoter region and VNTR in intron 2.
LPR: two (or sometimes three) alleles are reported: “long form” and “short form”.
VNTR/STin2: several alleles are reported, usually 9, 10, 12 repeats, denoted by STin2/9, etc.
LPR and VNTR are not in consistent linkage disequilibrium (LD). The LD is high in Europe but less in India and very low or zero in the Far East. The active locus is probably close to VNTR, but presumably a complex intragenic haplotype is really relevant, with the LPR and VNTR markers being very imperfect proxies. Nevertheless, the high expression/rapid clearance/low brain serotonin phenotype reportedly corresponds to the “long form” of LPR and to the STin2/12 repeat form of VNTR. The low expression/slow clearance/high brain serotonin corresponds to the “short form” of LPR, and presumably to the STin2/9 and STin2/10 forms of VNTR.
Our hypothesis is that an allele 5-HTT corresponding to low expression (high CNS serotonin) codes for trait P by dominant inheritance.
Thus, by being loose proxies our hypothesis is:
• LPR/long form, and STin12/12 are related to non-P trait
• LPR/short form, and STin12/9 & STin12/10 are related to P trait
Conditions related to trait non-P
ADHD and long allele
ADHD and long allele in Germany
ADHD and STin2/12 in Corybantic Calcutta (note weak LD between LPR and STin2)
Impulsive (vs. non-impulsive) Korean prisoners had higher frequency of long allele
Conditions related to trait P
KO Mouse (low expression) gives low aggression
Lower Impulsivity with short allele
Autism (multiple studies) trends to short allele
Obsessive-compulsive behavior, depression and short allele in Sweden
Perfectionism and Post-partum Depression and short allele
Post-partum Depression and short allele
“Two studies regarding symmetry, and compulsions involving repeating, counting, and ordering/arranging” and short allele
Persistence and COMT in normal subjects
Fibromyalgia: Persistence and Harm Avoidance, and short allele
Anorexia nervosa and short allele
“Negative Affectivity” and short allele
Depression, Germany and short allele
Unipolar depression (severe) in women and short allele
Depression in girls, Britain and short allele
Social Phobia and short allele
Shyness and short allele
Migraine and short allele
Migraine and STin2/10 allele
Panic disorder and complex haplotype
Schizophrenia risk and trend to STin2/12 allele
Our hypothesis is that 5-HTT “codes” for the P trait. But we do not rule out that other genes are significantly involved in expression of the P trait as well."
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