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With the issue of replication in mind, I was interested to read the Letter to the Editor from Robinson and colleagues* (open-access) who set about trying to replicate the findings from Skafidas and colleagues** (open-access) and their notion that science might be making some in-roads into the detection of "genetic biomarkers [that] can correctly classify ASD from non-ASD individuals". I posted about the Skafidas study at the time also (see here) and their analysis of single-nucleotide polymorphisms (SNPs) in relation to autism spectrum disorder (ASD).
The Robinson letter reports an attempt to replicate the Skafidas findings based on an independent analysis of data from the Psychiatric Genomics Consortium (PGC) "which includes ~5400 cases, more than three times the number used in the original [Skafidas] report". I'm not on this occasions going to get the fine-toothed comb out on both papers because they're open-access so free for anyone to read.
The conclusions from Robinson et al are pretty clear: "We find no evidence that the implicated SNPs, the classifier or the pathways named in Skafidas et al.1 are associated with ASDs. We therefore conclude that the classifier, as presented, cannot be used in a general way to predict ASDs, and consequently is unlikely to have any translational value."
Obviously such findings are both a blow to autism research and also the original authors who first proposed the classifier model, who I don't doubt probably invested quite a lot of time, effort and funds into getting their experiments done and results published (and published in a Nature journal). The ego also takes a bit of a knock under such circumstances, believe me (see here and here and here).
The Robinson data however re-emphasize the importance of replication in autism research. Perhaps just as important, they also reaffirm that autism is a tremendously difficult set of conditions to study. As is often the case when it comes to a heterogeneous condition like autism (or should that be the autisms) often carrying more than its fair share of comorbidity (see here) including risk of certain somatic conditions (see here), consistent findings are often few and far between. Indeed, that the use of the label autism, whilst providing a way of classifying certain types of behaviour and their impact on a person's life, is not necessarily the best thing for research purposes, as was vocalised through the grudge match that was DSM V vs. RDoC (see here).
The added realisation that outside of no one single SNP being linked to all autism (see here) there may be a significant degree of overlap when it comes to the genetics of the autisms with other developmental and psychiatrically defined conditions (see here) implies that it's going to be some time yet before any genetic biomarkers or test is going to be able to accurately classify autism, sorry the autisms with any great accuracy. Then there is the question of what such a test would accomplish. I've not even mentioned the fact that autism, whilst having a genetic component, is probably not without it's [variable] partner in crime, environment (however you want to define this) when it comes to aetiology. And don't even mention that other area of increasing interest, epigenomics (see here)... which in recent days has seen some interesting papers published (see here and see here).
I suppose in the spirit of all this talk on replication, the last question should be: who next is going to try and replicate the Robinson results? Indeed, does science any longer need the 'Letter to the Editor' in light of the rolling out of PubMed Commons?
* Robinson EB. et al. Response to ‘Predicting the diagnosis of autism spectrum disorder using gene pathway analysis’. Molecular Pyschiatry. 2013: Oct 22. doi: 10.1038/mp.2013.125
** Skafidas E. et al. Predicting the diagnosis of autism spectrum disorder using gene pathway analysis. Molecular Psychiatry. 2013; Sep 11. doi: 10.1038/mp.2012.126
E B Robinson, D Howrigan, J Yang, S Ripke, V Anttila, L E Duncan, L Jostins, J C Barrett, S E Medland, D G MacArthur, G Breen, M C O'Donovan, N R Wray, B Devlin, M J Daly, P M Visscher, P F Sullivan, B M Neale (2013). Response to ‘Predicting the diagnosis of autism spectrum disorder using gene pathway analysis’ Molecular Psychiatry DOI: 10.1038/mp.2013.125