A problem in genome-wide association studies (“GWAS”) is the”missing heritability” issue–identified genetic variation can only account for a small fraction of the estimated genetic contribution to variation in that trait. Razib has a good roundup of several explanations (and I added some speculation about nearly-neutral mutations).
GWAS also have problems accurately characterizing the trait. For example, not all heart diseases (note the plural) are alike, so we have to be certain that we accurately assess the trait of interest. But what is very rarely discussed is the environmental component of heritability in GWAS. In fact, to me, the absence of accurate environmental characterization is potentially a huge problem for GWAS, to the point that I called it something the field has forgotten:
Heritability estimates are always environment-dependent. When the edifice of quantitative genetics was being developed (by Falconer and others), it relied heavily on agriculture (and agriculture was the main ‘consumer’). This provided a large body of empirical knowledge that made it impossible to forget that even small differences in environment can affect the strength of heritability estimates (as well as the type of correlations between traits–but that’s another argument all together). Human genetics in particular, which often does is piss-poor job of quantifying the environment (or incorrectly assumes that twin studies control for this effect) seems, to me, vulnerable to this.
Secondly, these studies are made on “natural” human populations. One thing we sometimes forget when doing these studies is that the results are specific to the environment they are measured in. I have mainly worked with data collected in the laboratory, and we always have to remember that the lab is not the same as the field; it’s a different environment. So, even if in the observed environment variation in ADHD prevalence may mainly be genetic, that does not mean that we can’t change the environment beyond what was in these studies to reduce the overall prevalence: for example we could reduce poverty and create a more equitable society where all genes will feel equal and will be able to live out their socialist selfish existence. Even if the poor were to be “genetic mud”, that wouldn’t mean their lives couldn’t be improved and Great Things be encouraged to sprout from their fertile genetic soil.
I would take this further and argue that, until we characterize the environment more rigorously–and healthy and diseased isn’t going to cut it–we have to treat many of these heritability estimates, and the attempts to explain the underlying contributions of genes, as speculative.