A new paper in Nature reports the results of a large genome-wide association of autism. After some fairly heroic data analysis, the researchers have managed to tag one region of the genome as containing a common variant that contribute to the disease, with odds ratios on the order of 1.2 (the paper actually reports six variants in the same region, but these all appear to be tagging the same underlying causal variant).
The finding is getting fairly glowing press coverage, but let’s keep it in context: an odds ratio of 1.2 means that individuals carrying the variant have their risk of the disease increased by around 20%; their probability of actually suffering from autism is still much less than 1%. This is not a finding that will lead to powerful new diagnostic tools for the early detection of autism, and it’s consistent with a generally fairly disappointing yield from studies of common variants in psychiatric diseases.
While the new variant is unlikely to have much utility for risk prediction, it should provide some insight into the molecular mechanisms of autism (and there is some good preliminary work in the paper heading in this direction). However, the biggest lesson from the paper is simple: the hunt for common variants underlying psychiatric diseases remains largely an exercise in frustration. This was a whole lot of work for a very slender yield in terms of potential causative variants.
Several recent studies (including one from the same group in the very same issue of Nature) have had much better luck looking at a different type of genetic variant: rare but large insertions or deletions of DNA, known as copy number variants. It seems likely that other types of rare variants – much smaller events, largely invisible to current genome scan approaches – will play an important role in the etiology of this disease.
This study was certainly worth performing, and the mechanistic work on the associated region will be interesting to follow – but autism may be one case where the advice of David Goldstein to abandon genome-wide association studies in favour of large-scale sequencing may be worth following as soon as possible.
Coverage elsewhere: Ed Yong has a characteristically thorough run-down on the paper, expanding on a number of important points I haven’t covered here.
(As an aside: New Scientist goes with the somewhat misleading headline “Gene variant found in 65% of autism cases“, which appears to be based on a quote from lead author Hakor Hakonarson (whose back story is an intriguing tale in itself). That headline might give the impression that this variant actually causes 65% of autism cases, which is absolutely not the case: if you read a little further down you will discover that the variant is also present in 60% of healthy controls.)