Much has been written about the so called “warrior gene” MAOA, also sometimes not as diplomatically referred to as the Psycho gene. We all carry this gene but certain mutations in these genes have been linked to an increased risk of violence, especially when there has been early life abuse [R]. First made famous by the story of a Dutch family with a history of violence, a court in Italy made headlines when it commuted the sentence of a violent criminal after it was found that he carried the variant of MAOA associated with aggression [R].
Myth 1: The MAOA “warrior gene” is rare.
Fact: We all carry the MAOA gene, just some of us have a form which may be linked with aggression. The alleles connected with aggression are carried by approximately 33% of the population, so if it’s just the MAOA genetic variant that makes us “warriors,” then there are lots of warriors running around out there .
But trying to explain behaviour based on a single gene is a tricky business, as there are many other environmental and physiological factors that define who we are. So lets have a look and see if the science stacks up, and see if we can bust some myths at the same time.
Monoamine oxidase (MAO-A)
The MAOA gene codes for an enzyme named Monoamine oxidase. Monoamine oxidase breaks down neurotransmitters such as noradrenaline, adrenaline, serotonin and dopamine, and as such, plays an important role in regulating mood. Located on the X chromosome women can be heterozygous or homozygous for MAOA (as women have two X chromosomes), whereas men only carry one copy (as they have one X and one Y sex chromosome) and are therefore hemizygous.
Myth 2: Men can be heterozygous for MAOA.
Fact: Men only have one X chromosome, so can only have one copy of the MAOA gene.
The Genetics of MAOA
MAOA is interesting as changes in its activity don’t relate to individual SNPs, rather they are driven by changes in its promoter region. All genes have a promoter region, which sit upstream of the gene in the DNA sequence and this is the location where polymerase proteins bind and begin to read through the gene.
Within the promoter of MAOA is a region of DNA known as a variable number tandem repeat or VNTR. VNTRs are small sequences of DNA which can be repeated a variety of times, which gives rise to the 2R or 3R terminology you may have seen around MAOA. 2R means that there are two repeat sequences in the VNTR, 3R three repeat sequences and so on. This is important as the number of repeats has a big impact on how well MAOA is “read” by the polymerase protein. When the gene is not read as efficiently not as much MAO-A is produced meaning the breakdown of neurotransmitters is also reduced [R]. It is this lack of MAO-A enzyme activity which is thought to lead to increased aggressive behaviour [R].
Myth 3: The aggressiveness associated with the “warrior gene” is caused by SNPs.
Fact: Changes in MAOA function are actually linked to alterations in the VNTR located in the promoter region.
I’ve summarised the common repeats below and how they impact on the efficiency of MAOA reading and thus MAO-A activity. 3.5R and 4R variants are thought of as normal, with 2R variants having the most reduced function and 3R and 5R variants sitting between. As such the 2R, 3R and 5R types are sometimes referred to as MAOA-L meaning low activity [R, R].
|VNTR Number (R)||MAO-A Activity||Risk of aggressive behaviour|
What effect do changes in MAOA VNTR have on aggressiveness?
Low activity of MAO-A is thought to drive increased aggressiveness. But if you look at the table above you can see the 3R form of MAOA is actually very common. I don’t know about you but upwards of 30% of the population being overly aggressive sounds very high.
So lets look at the data; the 2R, 3R and 5R variants which show reduced MAO-A enzyme activity have been linked with increased aggressiveness in a variety of studies [R, R]. So far the hypothesis seems to be holding together.
But! all these reports come with a very large caveat. Whilst they do show that the MAOA-L forms are associated with increased aggression, having an MAOA-L form does not mean that someone will be aggressive, there are numerous other factors associated, with the most important thought to be early life abuse [R].
Simply put, whilst some people with the 2R, 3R and 5R variants were more aggressive, there were lots of people who also had these variants who weren’t more aggressive. The associations only appeared when a large enough population was studied, and this suggests that there are lots of other factors which are also influencing how aggressive we are, not just MAOA. Some studies have failed to find a link between MAOA and aggression [R].
Myth 4: Having less active MAO-A will make you more aggressive.
Fact: Having less active MAO-A may make you more aggressive, but there are many other factors that also influence this.
It is very desirable to paint a simple picture, but understanding how genetics and behavior interact is very, very complicated, and unpicking the contribution of MAOA-L to increased aggression is very difficult, which I’ve summarised in the image below.
Understanding the contribution of MAOA-L to increased aggression is difficult, as many other factors play important role. Whilst option a) may be most desirable to us as an easy to understand relationship b) is actually more accurate.
Can I find out if I’m MAOA-L?
The final important question is can you find out what form of MAOA you have using genetic tests like 23andMe? Well as mentioned above, alterations in MAOA function are to do with changes in the number of repeats in the VNTR, this can be detected by sequencing your genome. 23andMe doesn’t sequence your entire genome, rather they look at key points of interest in your genome. The reason for this is cost and time, whilst getting cheaper and faster all the time, the cost to sequence your entire genome is still out of the reach of most consumers.
But, there are some things you can look at. Linkage disequilibrium is the complicated sounding term which is used when two separate regions of the genome are associated with each other more or less often than would be expected by chance. Say we’re interested in allele A; we know allele A is in linkage disequilibrium with allele B but we aren’t able to detect allele A. But if we were able to detect allele B we could then assume that allele A was also present.
Interestingly there are several SNPS which are in linkage disequilibrium with the different forms of MAOA. I’ve detailed these in the table below, if you have the risk allele for one of the linked SNPs then you are likely to have the associated VNTR, but this is not definite, the only way to know for sure would be to directly analyse your MAOA gene.
So for example those with the rs909525 ‘C’ allele are likely to have 3 repeats within the MAOA VNTR (3R) [R, R]. Importantly, the proxy for 5R requires that you have all three of the risk alleles below rs909525 ‘C’, rs3027399 ‘G’ and rs6323 ‘T’. There currently isn’t a proxy SNP available for the 2R form although this is very rare.
Myth 5: Consumer genotyping like 23andMe can tell me my MAOA status.
Fact: There are some SNPs that associate with certain MAOA forms, but the only way to know for sure is to directly analyse MAOA.
|SNP ID||Major allele/Minor allele (Risk)||Risk allele "Warrior"?||% of population with risk allele|
|rs909525||T/C||Y (3R, 5R*)||43%|
The SNPs above are in linkage disequilibrium with the marked MAOA VNTR, so if you carry the risk allele you are likely to also carry the associated VNTR [R, R]. *In linkage disequilibrium only when all three risk alleles are present.
To sum everything up the interaction between genetics and behaviour is very, very complex to put it mildly. Whilst it is very easy to make bold statements such as “low MAO-A activity leads to increased aggressiveness”, a modern day of equivalent “of a pill for every ill”the reality is much less clear.
Whilst there is definitely an association with the 2R, 3R and 5R forms of MAOA and increased aggression, the actual contribution of MAOA is unknown, but most likely low [R].
If you’re interested in understanding your MAOA status the SNPs described above can act as a good proxy, but for true accuracy you would have to get your MAOA gene sequenced.