SSC SNP picks

er, ... no ... .

I mentioned in my previous post that you could link a SNP (eg rs4570625) to your own 23andMe results using a link like this:

https://www.23andme.com/you/explorer/snp/?snp_name=rs4570625

Scott Alexander at the almost-always-reliable* Slate Star Codex wrote (November 2014) this amusing post "How To Use 23andMe Irresponsibly" describing his favourite SNPs.

Well, now they're my favourites too and I copy his (lightly edited) thoughts below, but with the SNP references switched from his choice - SNPedia - to my choice, 23andMe.

Quick reminder: most traits in life are quantitative, they come in degree, not kind. In the human genome they are polygenic - many SNPs are involved (and other genetic mechanisms too) .. so one SNP is hardly going to be decisive. In most cases.

--- How To Use 23andMe Irresponsibly - (from SSC)  ---

"rs909525 is linked to the so-called “warrior gene” which I blogged about in the last links roundup. People with the normal four or five repeat version of these gene are less violent than people with the three-repeat version, and people with the two-repeat version are massively overrepresented among violent criminals. ... Although this SNP isn’t the warrior gene itself, it’s linked to it closely enough to be a good predictor.

"This is on the X chromosome, so men will only have one copy (I wonder how much of the increased propensity to violence in men this explains). It’s also one of the minus strand ones, so it’ll be the reverse of what SNPedia is telling you. If you’ve got T, you’re normal. If you’ve got C, you’re a “warrior”. I’ve got C, which gives a pretty good upper limit on how much you should trust these SNPs, since I’m about the least violent person you’ll ever meet. But who knows? Maybe I’m just waiting to snap. Post something dumb about race or gender in the open thread one more time, I dare you…"

I'm T and my mother, Beryl Seel was (T;T), both .. normally unwarlike.

"rs53576 in the OXTR gene is related to the oxytocin receptor, which frequently gets good press as “the cuddle hormone” and “the trust hormone”. Unsurprisingly, the polymorphism is related to emotional warmth, gregariousness versus loneliness, and (intriguingly) ability to pick out conversations in noisy areas.

"23andMe reads this one off the plus strand, so your results should directly correspond to SNPedia’s – (G;G) means more empathy and sociability and is present in 50% of the population, anything else means less. I’m (A;G), which I guess explains my generally hateful and misanthropic outlook on life, plus why I can never hear anyone in crowded bars."

We're both (G;G) which makes us kind and empathic ... .

"rs4680 is in the COMT gene, which codes for catechol-o-methyltransferase, an enzyme that degrades various chemicals including dopamine. Riffing on the more famous “warrior gene”, somebody with a terrible sense of humor named this one the “worrier gene”.

"One version seems to produce more anxiety but slightly better memory and attention; the other version seems to produce calm and resiliency but with a little bit worse memory and attention. (A;A) is smart and anxious, (G;G) is dumb and calm, (A;G) is in between. if you check the SNPedia page, you can also find ten zillion studies on which drugs you are slightly more likely to become addicted to. ..."

Both of us are (A;G) which makes us average and average.

"rs7632287, also in the oxytocin receptor, has been completely proportionally and without any hype declared by the media to be “the divorce gene”. To be fair, this is based on some pretty good Swedish studies finding that women with a certain allele were more often to have reported “marital crisis with the threat of divorce” in the past year (p = 0.003, but the absolute numbers were only 11% of women with one allele vs. 16% of women with the other). This actually sort of checks out, since oxytocin is related to pair bonding. If I’m reading the article right (G;G) is lower divorce risk, (A;A) and (A;G) are higher – but this may only apply to women."

Both my mother and I are (A;G) which makes her a bit .. flighty?

"rs11174811 is in the AVPR1A gene, part of a receptor for a chemical called vasopressin which is very similar to oxytocin. In case you expected men to get away without a divorce gene, this site has been associated with spousal satisfaction in men. Although the paper is extremely cryptic, I think (A;A) or (A;C) means higher spousal satisfaction than (C;C). But if I’m wrong, no problem – another study got the opposite results."

I'm (C;C) as was my mother, Beryl Seel, which means .. probably nothing.

"rs25531 is on the serotonin transporter. It's Overhyped Media Name is “the orchid gene”, on the basis of a theory that children with one allele have higher variance – that is, if they have nice, happy childhoods with plenty of care and support they will bloom to become beautiful orchids, but if they have bad childhoods they will be completely screwed up. The other allele will do moderately well regardless. (T;T) is orchid, (C;C) is moderately fine no matter what. There are rumors going around that 23andMe screwed this one up and nearly everybody is listed as (C;C)."

For my mother and myself, 23andMe did not report on this one.

"rs1800955 is in DRD4, a dopamine receptor gene. It's overhyped media name is The Adventure Gene, and supposedly one allele means you’re much more attracted to novelty and adventure. And by “novelty and adventure”, they mean lots and lots of recreational drugs. This one has survived a meta-analytic review. (T;T) is normal, (C;C) is slightly more novelty seeking and prone to drug addiction."

I was not genotyped at this location and my mother, Beryl Seel was (C;T) which made her a little bit adventurous with lots of use of recreational sherry.

"rs2760118, in a gene producing an obscure enzyme called succinate semialdehyde dehydrogenase, is a nice polymorphism to have. According to this article, it makes you smarter and can be associated with up to fifteen years longer life (warning: impressive result means almost certain failure to replicate). (C;C) or (C;T) means you’re smarter and can expect to live longer; (T;T) better start looking at coffins sooner rather than later."

I'm (T;T) and my mother, Beryl Seel was (C;T) which makes me resigned to an early grave. She lived to 92.

"rs6311 is not going to let me blame the media for its particular form of hype. The official published scientific paper on it is called “The Secret Ingredient for Social Success of Young Males: A Functional Polymorphism in the 5HT2A Serotonin Receptor Gene”.

"Boys with (A;A) are less popular than those with (G;G), with (A;G) in between – the effect seems to be partly mediated by rule-breaking behavior, aggression, and number of female friends. Now it kind of looks to me like they’re just taking proxies for popularity here, but maybe that’s just what an (A;A) nerd like me would say. Anyway, at least I have some compensation – the popular (G;G) guys are 3.6x more likely to experience sexual side effects when taking SSRI antidepressants."

I'm (G;G) and my mother, Beryl Seel was (G;A) which makes me out to be some kind of bad boy!? I must remember to keep off those SSRI tablets.

"rs6265, known as Val66Met to its friends, is part of the important depression-linked BDNF system. It’s a bit depressing itself, in that it is linked to an ability not to become depressed when subjected to “persistent social defeat”. The majority of whites have (G;G) – the minority with (A;A) or (A;G) are harder to depress, but more introverted and worse at motor skills."

I predicted I would be (A;A) based on poor motor skills and in fact I'm (A;G). My mother, Beryl Seel was the normal (G;G) which is consistent with her not-bad motor skills (except at driving).

"rs41310927 is so cutting-edge it’s not even in SNPedia yet. But these people noticed that a certain version was heavily selected for in certain ethnic groups, especially Chinese, and tried to figure out what those ethnic groups had in common.

"The answer they came up with was “tonal languages”, so they tested to see if the gene improved ability to detect tones, and sure enough they claimed that in experiments people with a certain allele were better able to distinguish and understand them. Usual caveats apply, but if you want to believe, (G;G) is highest ability to differentiate tones, (A;A) is lowest ability to differentiate tones. (A;G) is in between.

Sure enough, I’m (A;A). All you people who tried to teach me Chinese tonology, I FRICKIN’ TOLD YOU ALL OF THE WORDS YOU WERE TELLING ME SOUNDED ALIKE."

Both of us test (A;G) so I'm sure we would have struggled with Mandarin, a daily requirement in Bristol.

So, just to reiterate, if you have a 23andMe account, click on the rs... links and see how you scored.

---

* If you care, I don't share his worries about the existential threat of the 'new AI'.

MAO-A: violence through to depression

From BBC News today:

"A genetic analysis of almost 900 offenders in Finland has revealed two genes associated with violent crime. Those with the genes were 13 times more likely to have a history of repeated violent behaviour. The authors of the study, published in the journal Molecular Psychiatry, said at least 5-10% of all violent crime in Finland could be attributed to individuals with these genotypes.
...
"Each criminal was given a profile based on their offences, categorising them into violent or non-violent. The association between genes and previous behaviour was strongest for the 78 who fitted the "extremely violent offender" profile. This group had committed a total of 1,154 murders, manslaughters, attempted homicides or batteries. A replication group of 114 criminals had all committed at least one murder. These all carried a low-activity version of the MAO-A gene, which previous research has dubbed the "warrior gene" because of its link to aggressive behaviour."

Monoamine oxidase A, also known as MAO-A, is an enzyme encoded by the MAO-A gene. It operates in nerve tissue where it degrades neurotransmitters such as dopamine, norepinephrine, and serotonin. This affects mood.

This "warrior gene" thing is somewhat old news. Wikipedia states (in a rather badly-written article):

"In humans, there is a 30-base repeat sequence repeated in one of several different numbers of times in the promoter region of the gene coding for MAO-A. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant. An association between the 2R allele of the Variable Number Tandem Repeat region of the gene and an increase in the likelihood of committing serious crime or violence has been found.

"MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34% in patients with major depressive disorder. Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females, depressed suicide in males, major depression and sleep disturbance in males and major depressive disorder in both males and females.
...
"The frequency distribution of variants of the MAO-A gene differs between ethnic groups. 59% of Black men, 54% of Chinese men, 56% of Maori men, and 34% of Caucasian men carry the 3R allele. 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men carry the 2R allele.

"A connection between a version of the monoamine oxidase A gene (3R) and several types of antisocial behaviour has been found. MAO-A had no statistically significant main effect on antisocial behaviour. Maltreated children with genes causing high levels of MAO-A were less likely to develop antisocial behaviour. Low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult. High testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ can also trigger violent behaviour in men with the low-activity alleles (which are overwhelmingly the 3R allele).

"In individuals with the low activity MAO-A gene, when faced with social exclusion or ostracism showed higher levels of aggression than individuals with the high activity MAO-A gene. Low activity MAO-A could significantly predict aggressive behaviour in a high provocation situation, but was less associated with aggression in a low provocation situation. Individuals with the low activity variant of the MAO-A gene were just as likely as participants with the high activity variant to retaliate when the loss was small. However, they were more likely to retaliate and with greater force when the loss was large."

So to summarise and over-simplify: low levels of MAO-A lead to aggression; high levels lead to depression.

Egocentricity asserted itself at this point and my thoughts turned to my 23andMe genotype data. The 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence aren't looked at by 23andMe, as they only test for SNPs. However, the gene which codes for MAO-A also has alleles which differ in SNPs, specifically rs6323.

Only one nucleotide to report here for me as it's on the X-chromosome and I'm male. The variant which expresses the most MAO-A is the G-variant, which makes its carrier prone to depression.

I'm T: so a tiny bit more warrior than someone on antidepressants.