Common variant for anxiety
Studies that look for an association between a genetic variant and a trait are often inconsistent, finding an association in some studies or some populations, but not others. This could be for a number of reasons– small samples sizes, heterogeneity, or difficulty quantifying the trait, among other things. Or it could simply be that there’s no association to find.
However, it’s certainly strong evidence for an association if inducing the variant allele in a mouse also induces the trait you’re looking at. This paper does an excellent job of that, pretty much conclusively settling the issue of whether a variant in a certain brain-expressed gene is invloved in anxiety. Mice without the variant are normal, mice with the variant display more anxious behavior (avoiding the middle of an open area, for example). Simple as that.
The causal allele is present at a frequency of 20-30% in Caucasian populations, so it is perhaps a large contributor to normal human variation in anxiety. And it’s also perhaps a prelude to finding common alleles that explain some of the variation of other cognitive phenotypes.
This could be for a number of reasons– small samples sizes, heterogeneity, or difficulty quantifying the trait, among other things.
In the Caspi et al (2003) study that the authors cite, as in many others, they used a diagnostic tool based on the DSM-IV, a psychiatric manual. Unfortunately, the DSM’s traits are categorical (i.e., if you do/don’t meet X out of Y criteria, you are/aren’t in group Z), unlike the continuous measures of personality traits you find in the Eysenckian EPQ, “Big Five” NEO-PI, Cattell’s 16PF, etc. More, the DSM-derived criteria are based on the extremes of a distribution — like suicide attempts. Such gravely fitness-reducing behavior surely has a larger environmental component (infection, tragic life event, etc.) compared to more normal behaviors like how frequently you feel on-edge, how outgoing you are, etc.
Presumably the genetic component of the variance would increase if people bothered looking at normal behavior, rather than the genetic causes of suicidal behavior, on the understanding that the extreme cases like suicides are tail-cases of normal distributions along with an even stronger environmental influence. As far as anxiety goes, what you would do is test for the allele’s effect size on the person’s Extraversion and Neuroticism scores from any of the above measurements of normal personality. Serious anxiety, major depression, etc., are associated with low Extraversion and high Neuroticism (“melancholics” in Galen’s typology). Such people prefer to be left alone and focus their energy inward, but are emotionally volatile.
Another thing — unlike the sub-general factors of intelligence, which highly intercorrelate, personality factors like Extraversion and Neuroticism are orthogonal. So, when we ask why group X’s IQ was selected upward, we understand that there’s pretty much just one intelligence that increased, with the sub-general factors mostly going along for the ride (verbal, quantitative, what have you).
But when group X’s level of Neuroticism, say, is selected upward, we don’t know that there’s something fitness-enhancing about that thing by itself. As I said, anxiety, depression, etc., are the interaction of low-E and high-N, and other interesting phenotypes may be the interaction of other orthogonal factors — for example, sociopathic behavior combines low Agreeableness (low empathy, distrust of others) with low Conscientiousness (aimless, low sense of duty / order).
At my personal blog, I hazarded a guess about why there might have been selection for higher Neuroticism in females: combined with independently high Extraversion, it encourages exhibitionistic behavior, which would be fitness-enhancing for females in certain environments. http://akinokure.blogspot.com/2006/10/youtube-exhibitionism.html
I think the particular state in the US is more due to facultative than genetic strategies, since adolescent Anglo girls weren’t always as nakedly exhibitionistic as they are these days. But clearly where exhibitionism would make a difference in snatching up an alpha-male, there would be a pressure for females to have higher Extraversion and also higher Neuroticism. And males too, if they suceeded by exhibitionistic behavior.
But because E and N are orthogonal, high-N would only benefit those who also chanced to have high-E, while those who chanced to have low-E would suffer from depression, be overcome with anxiety, contemplate suicide more frequently, etc. Alleles favoring higher N would thus be like the sickle-cell allele, and researchers seeking to understand the benefit of depression or anxiety would be akin to those seeking to study the benefit of sickle-cell anemia (not to be mean, of course, just pointing it out to clear things up). High levels of depression, anxiety, etc., could merely reflect the ugly costs of high-N, while the outweighing benefits might be found in individuals who also were extraverted rather than introverted.
hm. anyone know the polymoprhic extent of BNDF in diff. populations? seems like this could be a candidate for why finnz are so fucked up….
Presumably the genetic component of the variance would increase if people bothered looking at normal behavior, rather than the genetic causes of suicidal behavior, on the understanding that the extreme cases like suicides are tail-cases of normal distributions along with an even stronger environmental influence.
ience.wiley.com/cgi-bin/abstract/105558613/ABSTRACT
agreed. there’s a trend now towards using continuous endophenotypes that underlie a binary trait in these sorts of studies now.
anyone know the polymoprhic extent of BNDF in diff. populations?
for the substitution associated with anxiety, I found:
japan: 41%
italy: 30%
usa: 18%
sorry to disappoint, but no data on the finns.
from here:
http://www3.intersc
jp, thanks.