In yesterday’s New York Times article, David Goldstein makes sense: he says “We’ve looked for common variants in schizophrenia and get almost nothing. This means natural selection has done a really good job of purging them away, and we’re left with rare variants, a constant flow of them, as the principal driver of the disease.”
Which is what any reasonable person thought a long time ago: the common disease-common variant notion never made much sense for a syndrome with a large impact on fitness. That genetic heterogeneity does not make drug development easier: even if the mutations cluster in certain pathways, reactivating a broken pathway may still require mutation-specific methods, which would sure take the profit out of drug development.
But the most interesting point in the article is Stefansson’s statement – “I would have thought the brain was a luxury organ when it comes to reproductive success.” That’s a weird thing to say. For one thing we known damn well that schiz strongly impacts fitness, even in contemporary society: the affected families dwindle away, which interferes with genetic studies.
More than that, does he really believe that being insane had no effect on reproductive success back in the Malthusian past? It’s hard to find a place more Malthusian than Iceland: does he think that crazy hardscrabble farmers did just as well as sane ones? Does he think that lunatics were just as likely to become godir and hornswoggle the neighbors out of their land?
The brain burns out 20% of our calories: does he think that could continue long under natural selection if there wasn’t a big payoff?
The answer is that he _does_ think all those absurd things: he doesn’t believe in ongoing natural selection in humans, particularly above the neck. I wonder why – but once we sequence him, maybe we’ll know.