Yet, many realize that GWAS and other omics, or idea-free methods, have provided a much lower yield than was promised or expected. This is expressed in terms like 'hidden heritability', referring to the familial clustering that should be genetic but for which specific genes cannot be found, or at least many individually trivial contributing genome regions are identified. In fact, this is what we should have expected, based on long-standing evolutionary theory and ideas about genetics. We've posted many, many times about this.
The evidence is consistent. Many genes interact to produce biological traits, in humans as well as other species including yeast and bacteria, and plants. These genes have to be regulated to control the timing and amount of their expression in cells, and gene regulation involves many interactions among genes and other DNA regions where regulatory proteins bind. Each of the functional DNA regions that are involved is subject to mutation that, if not lethal, can circulate in the population over generations.
This is known as 'polygenic' variation. The word simply means a great many contributing genetic elements that mainly have individually tiny effects. Findings from GWAS and other types of studies consistently point to evidence for just this kind of polygenic control. But the frustrating thing (for proponents of genetics-are-everything and of personalized genomic medicine, etc.) is that with many individually trivial contributions, each person's genotype is different and each case of the 'same' disease is due to different genotypes and/or environmental exposures.
At the same time, major mutational changes in contributing genes can yield a serious effect that proper analysis can assign to that specific gene. Our methods identify these, and we generally refer to their effects as 'Mendelian'. These are often due to changes that inactivate ('knock out') the gene. This success in easily identifying causes large and only problematically finding the small ones suggests that the reason there appears to be so much genetic control (reflected in measures like family correlation or heritability) is simply what we think it is: traits really are polygenic.
But can life be that complicated??
In the face of this apparent complexity--many argue that life can't really be that complex. One may feel that it's just not plausible that hundreds or thousands of genes can be the explanation for traits that show orderly value distributions in populations. That orderliness, and the relatively orderly nature of evolution, and the fact that a trait can be knocked out by single genes, all might be seen as indicating that life must have been able to evolve our complex traits in a way that is not so complex after all. We're just not understanding--yet!
The usual approach to this view is to argue that we just need longer, larger, costlier studies, or more kinds of 'omics' approaches--like epigenetics, copy number variation, nutrigenomic, microbiomic studies and the like. Then, this view goes, we'll (whew!) finally identify essentially all the causal elements. But if things really are polygenic, this may be hopeless.
But, do we really know what's going on, whether or not causation is totally enumerable as the current belief system holds? We know this belief system is based in part--perhaps major part--on the kinds of professional vested interests and paucity of better ideas that we write often about here. One way to view this is imply to assert, yet again, that for nearly a century we have had the right kinds of knowledge and the right interpretation, even if lacking in sufficient technology to document those ideas, and that recent technologies are showing just what we expected to find--despite the resistance to the contrary, the idea that we can reduce complexity to simple genetics, or even omics, is largely based on wishful thinking.
But what about an alternative?
If both sides of these issues are wrong, perhaps there is some other explanation for what seems like the tractable theory of life's coherence, something other than many tiny contributing factors. Could there be some force or factor--call it 'Fairy Dust'--that we simply have not discovered but that underlies what we are struggling to understand?
Such factors would be analogous to those that were discovered in other 'paradigm shifts', or revolutionary changes in scientific gestalt, that have happened over time. We might refer to quantum effects, dark energy or dark matter, gravity particles, and so on as exemplars of such factors in other sciences. It could be some kind of 'field' or 'force' whose nature we don't know of or even suspect. Or just another way of thinking about what we know already.
One can never deny the possibility that Fairy Dust exists. But neither can we propose studies to find it, as if we knew it existed, and it's understandable given human nature and the history of science that we'll press ahead, ever more intently, trying herd-like to force things to fit our theory, or trying to outwit our theory, the way that's par for the course now, until someone somehow stumbles on the insight required to identify the fairy dust and improve our biological explanations. This is just how Thomas Kuhn described the way science works (as we posted about yesterday).
But don't hold your breath, because to us, right now, it does not seem that our explanations are missing any such thing.