Not only do these results implicate common causal variants as the source of heritability in disease susceptibility, but they also suggest that gene-gene (epistasis) and gene-environment interactions are of limited impact. Both the genetic and environmental backgrounds for a particular allele vary across Eurasia, so replicability puts an upper limit on their influence. See also Epistasis vs Additivity.How can it be? But what about the marvelous incomprehensible beautiful sacred complexity of Nature? But But But ...
In the blood pressure (BP) study cited below, the data include East and South Asians, African Americans and Europeans. The effect sizes of variants in one population are well correlated with effect sizes in other populations, despite changes in the genetic background (i.e. other genes) and environments with which they interact. This suggests the interaction effects are small.
Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations
Abstract: ... We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.
(COGENT = African Americans, ICBP = European Americans)
Long live "beanbag genetics"! :-)
A Defense of Beanbag GeneticsSee also Eric, why so gloomy?
JBS Haldane
My friend Professor Ernst Mayr, of Harvard University, in his recent book Animal Species and Evolution1, which I find admirable, though I disagree with quite a lot of it, has the following sentences on page 263.
The Mendelian was apt to compare the genetic contents of a population to a bag full of colored beans. Mutation was the exchange of one kind of bean for another. This conceptualization has been referred to as “beanbag genetics”. Work in population and developmental genetics has shown, however, that the thinking of beanbag genetics is in many ways quite misleading. To consider genes as independent units is meaningless from the physiological as well as the evolutionary viewpoint. [Italics mine]... In another place2 Mayr made a more specific challenge. He stated that Fisher, Wright, and I “have worked out an impressive mathematical theory of genetical variaion and evolutionary change. But what, precisely, has been the contribution of this mathematical school to evolutionary theory, if I may be permitted to ask such a provocative question?” “However,” he continued in the next paragraph, “I should perhaps leave it to Fisher, Wright, and Haldane to point out what they consider their major contributions.” ...
Now, in the first place I deny that the mathematical theory of population genetics is at all impressive, at least to a mathematician. On the contrary, Wright, Fisher, and I all made simplifying assumptions which allowed us to pose problems soluble by the elementary mathematics at our disposal, and even then did not always fully solve the simple problems we set ourselves. Our mathematics may impress zoologists but do not greatly impress mathematicians. Let me give a simple example. ...
Fisher's Fundamental Theorem of Natural Selection identifies additive variance as the main driver of evolutionary change in the limit where selection timescales are much longer than recombination (e.g., due to sexual reproduction) timescales. Thus it is reasonable to expect that most of the change in genus Homo [traits which have been under selection] over the last millions of years is encoded in a linear genetic architecture.
