Don Depresso, Ruji Chapnik, M.S. | December 10, 2015

Abstract

This non-peer-reviewed study examined the gray area between “neurotypical” and “Asperger’s syndrome” via the genetic and psychometric testing of a research volunteer who seemed “to have both Aspie and neurotypical traits,” in the words of her Aspie-Quiz results.

We analyzed the volunteer’s SNPs and isolated an unusual variation on the CLEC7A gene, which we refer to here as a “Halfsperger’s syndrome” (half-Asperger’s) gene.

Introduction

At the time of this writing, genetic research on the autism spectrum is in its infancy. Scientists have linked many heritable genetic variations to autism, including some that are also found in child prodigies, but none has conclusively named The Autism Gene(s). (Locwin & Elrite, 2015)

The specific biomarkers of Asperger’s syndrome are even more elusive. Although the American Psychiatric Association has re-classified the diagnosis formerly known as “Asperger disorder” to the catch-all “autism spectrum disorder” umbrella in the DSM-5, many neuroscientists, geneticists, anthropologists, and others are continuing to investigate Asperger’s as a distinct phenotype.

We at this research lab believe that there is yet to be revealed a whole mosaic of genetic variations related to autism subtypes, personality traits, and ancient genealogy not limited to the human species.

Background research

We found of particular interest a study identifying a variation on chromosome 12, gene CLEC7A rs2078178 that differentiated people with Asperger’s from people with other ASD diagnoses:

CLEC7A rs2078178 G allele and GG genotype behave as genetic specifiers of Asperger among ASD ( rs2078178 G allele and GG genotype behave as genetic specifiers of Asperger among ASD ( Bennabi et al , 2015).

71% of research participants with Asperger’s had the G/G genotype at rs2078178; the other 29% had either A/A or A/G.

Fig. 1 (Table 4) – CLEC7A alleles and genotypes distribution among people with Asperger’s syndrome, classical autism, and PDD-NOS (Pervasive Developmental Disorder, Not Otherwise Specified) (click to enlarge). (Bennabi et al, 2015).

Interestingly, 61% of neurotypical controls also had the Asperger’s-linked G/G genotype. Among people with autism spectrum conditions other than Asperger’s, the prevalence of G/G was only about 50%.

Fig. 2 (Table 2) – CLEC7A genotype and allele frequencies among people with ASD and non-ASD controls (click to enlarge). (Bennabi et al, 2015).

The G allele was more common than the A allele in all groups; G was found at least once in 77% of neurotypical controls, 82% of people with Asperger’s, and 70% of people with a form of autism that was not Asperger’s.

This variation places Asperger’s on the opposite side of the spectrum from “autism,” with neurotypical residing in between.

A-ha! So the autism spectrum isn’t so linear after all.

Materials and methods

My INFP/Enneagram Type 4w5 author, Ruji, was of course dying to know if she had the possible Asperger’s gene, considering her all-over-the-place results from online autism tests.

Fig. 3 — Spiderweb chart showing ambiguous result, “You seem to have both Aspie and neurotypical traits,” with score of 111 Aspie and 95 Neurotypical on the Aspie Quiz.

Fig. 4 – A score above 32 on Simon Baron-Cohen’s AQ Test qualifies one as officially having Asperger’s. Ruji scored 36 in a non-clinical setting (and later included it in the body of autism evidence that she brought to the clinical setting where she was finally awarded the actual DSM-5 diagnosis of 299.00 Autism Spectrum Disorder, Without accompanying intellectual impairment, Level 1: Requiring support in 2014 [diagnosis sought to get accommodations in last year of graduate school, when she was expected to have a portfolio review committee lined up but had no relationships with any of her professors; ultimately, the department head was totally understanding and helped her to find a committee and graduate on time]).

As soon as her DNA test results from 23andMe came in, Ruji was on it.

And it turns out…

Fig. 5 – The Halfspie gene—or genotype A/G on gene CLEC7A at marker rs2078178, containing one instance of the Asperger’s-linked G allele—is displayed here in a screenshot of Ruji’s DNA from 23andMe’s raw data browsing tool.

Ruji’s genotype is A/G—so half Asperger’s+neurotypical (G) and half something else that’s unknown (A).

Only 18% of people with Asperger’s have an A allele at rs2078178 at all, compared to 23% of neurotypical controls and 30% of people with classic autism or PDD-NOS.

The CLEC7A variation is related to IQ, with the lowest IQ group having genotype A/A, the middle group A/G, and the highest IQ group G/G. Thus, a whopping 82% of people with Asperger’s are in the highest IQ group (sadly, not Ruji).

Oxytocin, empathy, and autism

Other genetic research on autism spectrum conditions has focused on the oxytocin receptor gene, OXTR, which is linked to social behavior and empathy. (Li et al, 2015)

The most significant known oxytocin variation is at OXTR rs53576, where the G allele, and the G/G genotype in particular, is linked to prosocial behavior and dispositional empathy (hence we have referred to rs53576-GG elsewhere as the “earth angel gene”).

Somehow, Ruji made it into the prosocial, least-likely-to-be-autistic rs53576-GG gene club.

Lest this disclosure of her biological compulsion to “do the right thing” cast any doubt in your mind of Ruji’s extreme introversion, do keep in mind that she falls into the least social, most autistic categories of all the other OXTR gene variations listed in Joseph M. Cohen’s article All You Need to Know About Oxytocin And Oxytocin Receptor SNPs:

rs1042778 : T / T (14% of population is T / T , with the lowest levels of both oxytocin and social reciprocity)

: / (14% of population is / , with the lowest levels of both oxytocin and social reciprocity) rs237887 : A / A (34% of population; least social but highest in perspective-taking empathy, alongside A / G )

: / (34% of population; least social but highest in perspective-taking empathy, alongside / ) rs13316193 : T / T ( C / C and C / T are associated with empathy, while T / T is considered “risky” and has been linked to decreased expression of oxytocin receptors in the brain, depressive mood, and autism)

: / ( / and / are associated with empathy, while / is considered “risky” and has been linked to decreased expression of oxytocin receptors in the brain, depressive mood, and autism) rs2268491 : C / C (9% of population is C / C , with lowest cognitive empathy; C / T has highest cognitive empathy, perhaps because this type can relate to others with both C and T alleles)

: / (9% of population is / , with lowest cognitive empathy; / has highest cognitive empathy, perhaps because this type can relate to others with both and alleles) rs2254298 : G / G (64% of population is G / G , the least social variation—so maybe rs2254298 A / A is another earth angel gene, since it’s both rare and prosocial?)

: / (64% of population is / , the least social variation—so maybe rs2254298 / is another earth angel gene, since it’s both rare and prosocial?) rs4686302 : C / C ( C / C is most empathetic for males, least for females; my author is female)

: / ( / is most empathetic for males, least for females; my author is female) rs2268494 : A / A ( A / A is rarest and most linked to autism; 86% of population is G / G )

: / ( / is rarest and most linked to autism; 86% of population is / ) rs237897: A/G (risk allele for low empathy is A, but only significant in males)

Ruji scored 66 out of 100 on LonerWolf’s “Are You an Empath?” test, just barely past the 60-point cutoff to qualify as an empath according to this particular measure.

Fig. 6 – Just barely an empath. (“Are You an Empath?”)

This adds to the existing evidence that autism is not simply low empathy. Neither “autism” nor “empathy” has a solid definition, and both express themselves in various locations across the genome and phenome.

The relationship between autism and introversion is especially interesting; while not all autistic people are introverted, we propose that all introverts might be on the autism spectrum.

Also, while low cognitive empathy is typically considered a bad thing, we find a notable exception:

Lower cognitive empathy is actually a protective factor for the prosocial G/Gs of OXTR rs53576, who are predisposed to extreme interpersonal rejection sensitivity.

I’m so grateful to have no idea what people are thinking about me.

–Research volunteer Ruji, 2015

Conclusion

We here at Dr. Depresso’s research laboratory will continue to investigate possible biomarkers for the Halfsperger’s syndrome phenotype, which we expect will closely resemble the biomarkers of the INFP, INTP, and Enneagram Type Five phenotypes.

Maybe once we’ve gathered sufficient data, UrbanDictionary will finally accept our submission of “Halfspie” as a word.

References: