
Where’s the heritability?
Biologists have at our disposal two major ways to assess how much genetics contributes to variation in the most interesting traits, or phenotypes, of our favorite study organisms—that is, the
heritability of those phenotypes.
There’s what you might call the “top-down” approach, under a classic quantitative genetics framework, in which we can measure a whole bunch of individuals with known pedigree relationships, then use some form of linear regression to ask how well that known pedigree predicts the phenotype of each individual—the extent to which individuals with closer relationships have more similar phenotypes is the extent to which genes contribute to that phenotype.
Alternatively, we can use genetic marker data coupled with planned crosses between selected indivdiuals in a quantitative trait locus (QTL) study, or, if controlled crosses aren’t feasible, a genome-wide association (GWA) analysis. These are more “bottom-up” approaches, because they identify discrete pieces of the genetic code that individually explain some fraction of the total phenotype variation within the sample. Add up all the effects of all those individual pieces, and maybe account for some interactions between them, and you should find that you explain just as much of the phenotypic variation as you would with a top-down approach.
Except, it turns out, that doesn’t often happen.
When researchers have gone looking for specific genetic loci underlying traits for which we already have well-established, robust top-down estimates of heritability, they find that they loci they can detect using either QTL or GWA methods don’t account for some—and sometimes a lot—of the known heritability. The classic example is human height. Top-down (heh) methods give height a
narrow-sense heritability—that is, the portion of heritable variation not due to interactions between loci or different variants at the same locus—of
more than 80%. Yet studies looking for specific loci responsible for height have explained much less than that—sometimes
as low as 5%.
Phenotypic variation, in other words, is left unexplained. This has made a lot of people very puzzled, and been widely regarded as a bad thing.
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