In the past decade, researchers have dramatically improved our understanding of the genetic basis of complex chronic diseases, such as Alzheimer's disease and type 2 diabetes, through more than 1,000 genome-wide association studies (GWAS). These scan the genomes of thousands of people for known genetic variants, to find out which are associated with a particular condition.
Yet the findings from such studies are likely to have less relevance than was previously thought for the world's population as a whole. Ninety-six per cent of subjects included in the GWAS conducted so far are people of European descent. And a recent Nature survey suggests that this bias is likely to persist in the upcoming efforts to sequence people's entire genomes.
Geneticists worldwide must investigate a much broader ensemble of populations, including racial and ethnic minorities. If we do not, a biased picture will emerge of which variants are important, and genomic medicine will largely benefit a privileged few.And success is always just out of reach -- if only. If only we have bigger samples, or more heterogeneous samples, or less heterogeneous samples, or more markers, or whole genomes.
The 'missing heritability problem' has led many to become dismissive of GWAS. A danger of this GWAS fatigue is that it deters others from applying the approach to populations where it is likely to yield excellent results. GWAS has proved most successful in relatively small homogeneous populations — in Finland, Iceland and Costa Rica, say, where people generally stay put. Large families and limited migration are common among populations in Latin America, Africa and South Asia — suggesting that new and important associations between diseases and regionally common genetic variants may be found easily in these groups.Well, yes, the ultimate in relatively homogeneous studies, family studies, have been quite successful in finding genes -- in cases of clearly genetic diseases. And it has been known for decades that different alleles or even different genes can lead to a similar phenotype. So it's no surprise that studies in isolated populations might yield results, but if they aren't usually generalizable beyond a single family or a small population, that isn't going to be widely useful. Nor have the genetic underpinnings of common chronic diseases been reliably or very usefully demonstrated, even in small homogeneous populations, so optimism about finding genes for diseases like heart disease or type 2 diabetes or asthma is pretty much unwarranted.
That said, including non-Europeans in medical studies is a laudable goal. And yes, genetic variation by geographic ancestry is to be expected. This was a point made in more than one journal paper by Ken many years ago when one-size-fits-all markers were touted as justification for the HapMap project....but it was an inconvenient, if obvious, truth that was ignored. The underlying reasons were not very savory and beyond this post.
So who is pushing this now? Geneticists who want to confirm their belief that GWAS work, that rare variants will explain the 'missing heritability' that isn't being captured by these studies now, and that all we need is bigger or more varied samples to prove it. And, pharmaceuticals pursuing the dream of the 'druggable' genome. And everyone who wants the largesse to continue pouring into this kind of science (which, not incidentally, will deprive other areas of funds, in the zero-sum game of research funding). One perhaps cannot blame the researchers for wanting research funds, or biotech firms wanting business, but nobody seems to be watching the priority store.
But even if the world is someday representatively sampled and included in genetic studies, "genomic medicine is going to largely benefit a privileged few" anyway. First to benefit will be the sequencers and the makers of the sequencers, and they will benefit handsomely, and direct to consumer genome-risk selling firms, followed by the analyzers of the resulting bioinformatics who will be able to mine the data, and apply for grants for follow-up studies when they don't get definitive answers, and then maybe (and, yes, hopefully!) a few people with clearly genetic diseases. Even in rich countries genomic medicine is going to remain unaffordable for most people for the foreseeable future -- trickle-down doesn't work here either. And that's assuming that there are benefits to be had! But, as we write about frequently here, widespread benefits of this kind of research haven't yet been demonstrated, and there are many reasons to believe they will be few and far between anyway, even at best.
Meanwhile, when it comes to public health, other avoidable disorders go under-attended. And once again we have to ask whether the largesse being showered on medical genomics could be better spent on prevention. As a colleague once said to us, it would be a lot cheaper to give everyone at risk of type 2 diabetes a personal trainer than to do all these genetic studies of the disease. And it would do people a lot more good! Studies of the genetics of T2D have been ongoing for 40 years -- including in non-European populations -- and have yet to yield significant results. Or prevent a single case of diabetes. Even sickle cell and ApoE related diseases are not yet very, if at all, solved in a way that is based on genotype data. Sickle cell was discovered more than a century ago. The promises of genetically based genomics may have been sincere, but they have proven to be hollow even in a medium term sense, despite various exceptions that one might cite. The thousands of GWAS hits are being misrepresented as such exceptions as a rule.
Pushing, exaggerating, and hyperbolizing expensive genetics research, even if it will get investiators interesting things study and subsidized visits to exotic places, is a highly, and usually knowingly cynical, way to lobby for funds (because this is often acknowledged in private). If one is as smart as a researcher at a privileged university, you could perhaps fairly be asked to use your intelligence to solve important problems on modest budgets and save the megabucks for real, proven public health improvements.
We suggest that we are at a point in our understanding of disease causation where lobbying for increased funding for genetic studies is simply to a great extent unethical.