Unravelling Quantitative Traits is Hard

I've said many times in the past that people who think they can say something deeply significant about the nature of phenotypical variation between "races" based only on the identification of a single allele of uncertain effect are at best fools and at worst liars, and this PLoS paper drives home the point I was making in a straightforward way; following is the synopsis.

Most of the differences in phenotype between unrelated members of a species are polygenic in nature. Because of their ubiquity and importance, these polygenic (or quantitative) traits have been intensively studied, and a variety of techniques have been proposed to identify and characterize quantitative trait genes (QTGs). Indeed, the main application of the recently published human HapMap project is to identify the genes responsible for diseases that are quantitative in nature. Using a well-defined Saccharomyces cerevisiae quantitative trait locus containing three QTGs (MKT1, END3, and RHO2), the authors used deletions to analyze the contributions of each gene to phenotype, singly and in combination, and found a variety of interactions. Expression analysis showed no difference in steady-state mRNA levels between alleles of the three genes. Homologous allele replacement identified the phenotypically relevant differences between alleles of each gene, which were single coding polymorphisms for two genes (MKT1 and END3) and the 3′ untranslated region of one gene (RHO2). Finally, analysis of multiple genetic backgrounds showed that the phenotypes conferred by these genetic variants were not conserved. The results show that the techniques proposed to identify QTGs, such as expression analysis and marker-trait association, have profound limitations, and that unbiased genome-wide approaches are needed to dissect quantitative traits. The results also demonstrate the complexity of the genetic interactions that affect quantitative traits and the value of the S. cerevisiae system in studying these traits.

Anyone who expects things to be easier with humans than they are with short-lived organisms for which no restrictions on experimentation exist is living in a dream world. It will likely take several decades to unravel the genetic basis for variation in such amorphous traits as "IQ" or personality, assuming it ever becomes possible at all, and anyone who claims otherwise is a charlatan selling snake oil.

PS: This abstract from a paper on common human diseases also presses home the same point - as much as population geneticists might wish it were otherwise, the evidence seems to indicate that epistasis is in fact a ubiquitous phenomenon, while complex interactions which defy simple "additive gene" expectations are almost certainly the rule rather than the exception. In plain English, don't expect any findings that some putative "IQ boosting alleles" can be found in some populations and not others to tell you anything whatsoever about their respective "innate" intellectual abilities; don't even assume that the existence of a single allele in multiple populations means that its effects need be the same in all of them.

Comments

[gene berman]

I am persuaded (and long before your excellent arguments) that "scientific" efforts to produce essentially different kinds of humans are misguided, not because tinkering (even successful tinkering) is impossible but because, apart from extremely limited applications (such as identifying potentiallly disastrous individual matchups of recessive alleles for undesirable conditions), the never-suspendable process of evolution actually works precisely as Dr. Pangloss would have us expect: for the best (and without requiring anyone to divine what that normative "best" might be).

A great many of the posters over at GNXP are inordinately focused on IQ. Whatever it means (and whatever the distribution over the world and between different groups of people) for general well-being, they seem entirely blind to the fact that the process of exchange (and of the dual competition between both buyers and sellers) by means of which all benefit from each others' specialized function, has as much potential for "smoothing out" welfare differentials as can possibly exist without reduction in total welfare. The discoveries of intellects such as Newton and Einstein made no difference whatever to general welfare in their times, while today, literally everyone on the planet is a direct beneficiary of their achievements. There seems general sentiment (at GNXP) that what the world really needs (replacing the good 5-cent cigar, still resonant with me) is genetic tinkering capable of moving the "bell"--of the curve--about 10 points to the right. That potential might be desirable but it might certainly NOT be. Just imagine a world in which sales, clerical work, bureaucratic timewasting employment, and lower-level technical and management abilities were even more greatly competitive and in which, more or less suddenly, far fewer were forced (by economic pressure and lack of educability for higher-level functions) into providing simpler, more physically-demanding performances. There's no doubt that things would "even out" under those circumstances--it just might not be in the way in which the IQ-tinkering proponents would expect (or whose result they'd like). But--not to worry--this too, shall not come to pass (though the same people will probably be saying the same stuff for a long time to come). My main objection is not to their ideas or their discussion--it's to the fact that, in the main, it's generally a (indiresct and sub-rosa) government-financed propaganda campaign, of the very sort the same types bemoan from the left (actually, they ARE of the left but simply don't recognize it--referring, in particular, to GC and similarly-inclined others).

Incidentally, Abiola, despite the fact that I've had virtually no education in Genetics (one-semester "survey" course in a state teacher-training college), I believe I have the unique distinction of being the only person--in the U.S., at least--ever disciplined (expelled, actually) for (among a list of things) insisting that fraud, corruption, and institutional coercion sufficed entirely to explain the Lysenko phenomenon; that was 1957. Those on the other side of that dispute weren't Lysenkoists in any sense--just good folks who insisted that people, especially scientists, didn't behave that way, no matter whether here or in that forward-looking commonwealth, the USSR. And, also noteworthy is that I predicted (at my disciplinary hearing) that the US would soon be embroiled in student rioting at campuses across the country; their "take" was that I was threatening them with violence (all I was doing was extrapolating from foreign news--I had no political affiliation nor even interest in those days).

[gene berman]

Note:

It occurred that my introductory comments might easily cause me to be mistaken as a believer in evolutionary meliorism. I'm not.
It's merely that whatever we see that IS (i.e., that which has survived) is, by definition, "fit" and for which we now seek explanation of the fait accompli in the environmental conditions to which such "fit" organisms have adapted. If there's a purpose to be divined, it's entirely summed (and described) in the single word "adaptation."
As long as change occurs, so will adaptation and a resultant (surviving) "fitness." Whether it's "good" or not is moot: it's the only. Que sera, sera.