00:00:00Is there a difference in heritability of antisocial behavior that's sexed?
00:00:09Do men inherit more accurately, is the heritability a greater effect on boys than it is on girls?
00:00:20Generally, no, but there's one exception that I want to come back to.
00:00:24So, what we see is that the genes that are associated with antisocial behavior in boys also affect girls.
00:00:33If you're female and you have a fraternal twin that's a male sibling,
00:00:39then his antisocial behavior predicts your likelihood of manifesting it,
00:00:45that the same liabilities are reflected in the same way.
00:00:52So, the same genetic liabilities make you more likely to be physically aggressive,
00:00:55they make you more likely to be relationally aggressive,
00:00:58they make you more likely to be substance using,
00:01:01they make you more likely to be risk-taking.
00:01:03It's just for everything the mean for men, the average for men is shifted up.
00:01:09So, the same impact would have a – sorry, the same raw materials would have a greater impact in real life?
00:01:15Yeah, yeah, yeah.
00:01:16The same way as women commit suicide – sorry, women attempt suicide more than men,
00:01:21but men commit suicide more than women.
00:01:23Their ability to enact violence, antisocial stuff tends to be greater, so it's magnified.
00:01:29And so, you know, part of that is around social opportunity.
00:01:33Like, for many years, you know, women were very discouraged from drinking,
00:01:38very discouraged from smoking, so you saw a big sex difference in smoking and drinking.
00:01:44Now, it's more socially acceptable for women to smoke and drink,
00:01:47and so that average difference has narrowed and it's the same genes that seem to be involved in VOE.
00:01:54The exception there is that most of our current studies have focused on what are called the autosomes.
00:01:59So, we have 23 pairs of chromosomes.
00:02:02One pair is the sex chromosomes, XY or XX, and typically developing children.
00:02:07And then the other 22 pair are the same across sexes.
00:02:13And nearly all of our contemporary studies have focused just on those 22 pairs of autosomes
00:02:19for kind of boring technical reasons that I'm not going to get into.
00:02:23We're just now really diving into the X chromosome to see is there something about the X chromosome
00:02:32that might have specific effects on antisocial behavior.
00:02:36And the reason why that's interesting is because men only have one X, whereas women have two.
00:02:41And so men are much more vulnerable to the effects of a genetic variant that's X-linked
00:02:48because they don't have another copy to compensate.
00:02:50Oh, that's so cool.
00:02:52So that's why colorblindness, for instance, is much more prevalent in men versus women
00:02:57because it's an X chromosome-linked genetic variant.
00:03:02That is so sick.
00:03:04So, the reason why we think the X chromosome might be important is,
00:03:11and again, just to back up a second, most of what we study in our lab is what we would
00:03:15call common genetic variation.
00:03:17So these are genetic differences between people that exist in at least 5%.
00:03:23Sometimes people say at least 1% of the population.
00:03:27The thing about common genetic variants is that they're common, which means that they
00:03:34are likely to have a relatively small effect in isolation because if they had a big effect,
00:03:40evolution would make them not common, would weed them out very quickly.
00:03:43So you have this trade-off between how common is a genetic variant and how big of an effect
00:03:48it is, how powerful it is.
00:03:50So what we're looking at is lots of common genetic variants, each of which have a tiny
00:03:55effect, but if you add them all up, then you get an appreciable effect, one that's meaningful.
00:04:01But there are studies of rare genetic variants, and there's one very famous study that was
00:04:06done in the 1990s where they looked at a rare variant on a gene on the X chromosome, and
00:04:16that gene was called MAOA.
00:04:18So your monoamines are how your neurons are talking to each other.
00:04:22It's like serotonin's a monoamine, dopamine's a monoamine.
00:04:26So monoamine oxidase is an enzyme that basically is like a Pac-Man eating the neurotransmitter
00:04:35in your brain.
00:04:36And if it doesn't work well, then you get this incredible buildup of the signals that
00:04:42your brain ordinarily uses to communicate with each other.
00:04:45Okay, so why is that important?
00:04:46In this one family where they found this genetic variant on the X chromosome, it made the MAOA
00:04:57enzyme not work, and all the men in that family suffered from extremely serious antisocial
00:05:04behavior problems, whereas their sisters were completely typically functioning.
00:05:10So the men, one raped his sister, one committed arson, one stabbed his boss with a pitchfork,
00:05:18huge levels of antisocial violence in this family.
00:05:22And their sisters and their moms were like, "What the fuck is going on here?
00:05:28Why do my sons and my brothers keep doing this, and we don't have this problem?"
00:05:34And it's because they have two Xs.
00:05:36And so if they inherited the mutation, it didn't matter, because there was another functioning
00:05:41version of the body to kind of dosage, like they could compensate for it.
00:05:47Whereas if you're a man and you only have one X and you got this 50/50 shot, which of
00:05:52your mom's Xs are you getting, it's a 50/50 shot whether or not you were going to be antisocial.
00:05:57So that's a rare variant.
00:06:00The vast majority of people who are deeply antisocial do not have this MAOA problem.
00:06:06Don't use the MAOA excuse.
00:06:08They can't use the MAOA excuse, but I think it's important for two reasons.
00:06:13And one is that we think of our moral faculties as our ability to not go around stabbing our
00:06:20boss every time we're mad at him in moral terms, in spiritual terms, or in cognitive
00:06:26terms.
00:06:28And it turns out that it's very vulnerable to disruption.
00:06:31You can change one letter of your genome that changes one gene, which changes one enzyme,
00:06:38and that capacity is really, if not destroyed, very, very impaired.
00:06:44And so the extent to which our morality is a biological faculty, I think, is very much
00:06:51supported by the fact that we can so profoundly disrupt it by this one change in our genome.
00:06:57And the other thing that I find so interesting about this case study is that these men were
00:07:04in the criminal legal system in the Netherlands, and no one was like, "Oh, this must be a
00:07:09genetic problem."
00:07:11They weren't not guilty by reason of insanity, they weren't lacking capacity to stand trial,
00:07:17they were indistinguishable from the rest of the offending population based just on their
00:07:23behavior.
00:07:24And the only reason we know that their behavior was due to this genetic cause is because of
00:07:31the familial data that made the pattern of transmission so clear.
00:07:37And I think that really brings up the question, how many other people who are persistently
00:07:42violent in families that are persistently violent, there might be some genetic or neurobiological
00:07:51explanation that we just haven't discovered yet, we just don't know that.
00:07:56In the '80s, they would have considered it ridiculous, this persistently violent family.
00:08:02You're telling me it's because they have one gene that's wrong?
00:08:05I would have seen it sounded like science fiction, but that was the case for this family.
00:08:11So we haven't, in modern genomics, turned our attention very often back to the X chromosome,
00:08:18but my lab is doing this now, and I'm really excited about this project.
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