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Posts Tagged ‘amygdala’

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Genes that confer risk for illness are ideal targets for prevention and treatment.  So, also, are genes associated with natural or treatment-based RECOVERY from illness.  In a search for “recovery genes”, association studies in women who have recovered from eating disorders (ED) vs. those who are still struggling to recover reveals that the C-allele of rs17536211 is associated with recovery.

From Bloss et al.:  “Given the substantial genetic component in the etiology of EDs in general, it follows that there may be genetic variants that contribute to the likelihood of recovery.”

“These were women who were over age 25 years, carried a lifetime diagnosis of either AN, BN, or ED-NOS (ie, subthreshold AN or BN), and for whom data were available regarding the presence (n=361 endorsed ongoing ED symptoms in the past year and considered ‘ill’) or absence (n=115 no ED symptoms in the past year and considered ‘recovered’) of ED symptoms.”

“rs17536211, an intronic SNP in GABRG1 on chromosome 4, showed the strongest statistical evidence of association with a GC-corrected p-value of 4.63 × 10−6, which corresponds to an FDR of 0.021 (Figure 1). The odds ratio (OR) observed for this SNP is 0.46, suggesting that possession of copies of the minor allele [C] is protective from long-term chronic illness (ie, it is associated with recovery).”

How might this SNP confer a protective effect?  The authors review data on the role of GABRG1 subunits in the un-learning of conditioned fear responses [“GABRG1 subunits are found in the lateral inputs, a region that arises from the intercalated cells masses, and is thought to be responsible for mediating inhibition of amygdala output during extinction of conditioned fear (Likhtik et al, 2008)”] and suggest that individuals with the protective C-alleles may be slightly more able to uncouple eating from a very real and debilitating fear response.

*photo credit

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Hey genome, why U make me stink at networking?

If only there was an allele that LESSENED the apprehensive and uncomfortable feelings I get when meeting new people.

As such negative feelings are the work of my amygdala, I’m wishing for some sort of LOSS-OF-FUNCTION allele that REDUCES the activity of neural circuits involved in the emotional processing of fear … but leaves other neural circuits untouched.

I just want something that takes the edge off new social experiences … yunno?

How about rs33977775 ? It contains a derived (as opposed to ancestral) T-allele that causes a Y135F change that disrupts the binding sites of the NPBWR1 receptor to its neuropeptide ligands (ie. LOSS-OF-FUNCTION).  Amazingly, this receptor has a restricted pattern of gene expression only among limbic circuits involved in emotion and reward processing (ie. EXPRESSED IN EMOTION PROCESSING CIRCUITS ONLY).

In their report, a team of authors measured the reactions of 126 university students to various social stimuli and report that individuals who carry one of these loss-of-function T-alleles (about 30% of the population) show a more positive response to social interactions.

“… the AT group perceived facial expressions more pleasantly than did the AA group, regardless of the category of facial expression. Statistical analysis … also showed that the AT group tended to feel less submissive to an angry face than did the AA group.”

So it seems that rs33977775 may dial down the amygdala response to social stimuli … just enough to ace the job interview, but not so much that you inappropriately hug your new boss. Nice!

Unfortunately, this SNP is not covered by 23andMe v3 and there is no report yet on linkage disequilibrium via 1000 genomes.  Since the frequency of the T-allele is low in African populations (1%) and about 10%-ish in other non-African populations, I guess the odds are that I’m an AA or AT.

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The article here:

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Dear Mrs. Jones,

The genetic profiling results show that your son carries 2 copies of the so-called “short” allele at the serotonin transporter linked polymorphic region (5-HTTLPR) and also 2 copies of the T allele of the G-703T polymorphism (rs4570625) in the tryptophan hydroxylase-2 (TPH2) gene.

Some studies find correlations between this genotype and higher amygdala activity – which, in turn – has been correlated with a number of anxiety-related traits and disorders.

In short, you may wish to expect that your son may grow up to be slightly more shy, bashful, diffident, inhibited, reticent, shrinking, hesitant, timid, apprehensive, nervous, wary, demure, coy, blushing, self-effacing, apprehensive, fearful, faint-hearted, wimpish, mousy, lily-livered, weak-kneed, unsure & doubtful.

Congratulations!  He will be a handful to raise as a child but one day make a great scientist, and an even better science blogger.


* thanks fyns for the pic.

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