"The era of personal genomic medicine may have to wait. The genetic analysis of common disease is turning out to be a lot more complex than expected.
Since the human genome was decoded in 2003, researchers have been developing a powerful method for comparing the genomes of patients and healthy people, with the hope of pinpointing the DNA changes responsible for common diseases.
This method, called a genomewide association study, has proved technically successful despite many skepticsâ€™ initial doubts. But it has been disappointing in that the kind of genetic variation it detects has turned out to explain surprisingly little of the genetic links to most diseases.
As Matt Ridley has said, no matter what you might think from reading the Health & Science section of your newspaper, your genes didn't evolve in order to kill you. So, this hunt for Killer Genes was always a little dubious, as I've been pointing out all decade.
Instead, your genes evolved to help you survive and reproduce. So, these expensive genome studies have so far proven better at finding the causes of differences in capabilities between individuals and between extended families (a.k.a., racial groups).
Dr. Goldstein argues that the genetic burden of common diseases must be mostly carried by large numbers of rare variants. In this theory, schizophrenia, say, would be caused by combinations of 1,000 rare genetic variants, not of 10 common genetic variants.
This would be bleak news for those who argue that the common variants detected so far, even if they explain only a small percentage of the risk, will nonetheless identify the biological pathways through which a disease emerges, and hence point to drugs that may correct the errant pathways. If hundreds of rare variants are involved in a disease, they may implicate too much of the bodyâ€™s biochemistry to be useful.
An alternative theory, proposed by Greg Cochran and Paul Ewald in the 1990s is that more diseases are caused by infections than we currently assume. (Here's the 1999 Atlantic Monthly cover story on them.) Of course, genes and germs are not mutually exclusive causes. It could be that, say, you'll only get Disease X if you are both exposed to Germ Y and your immune system lacks Gene Variant Z.