As the paper put it -
For simplex families, who have only a single affected individual in multiple generations, approximately 40% of liability traces to additive effects whereas this narrow-sense heritability exceeds 60% for ASD individuals from multiplex families.Or to put that another way, you can only blame genetic mutations for roughly half the risk of autism. This idea isn't necessarily new but it is the first time that I have seen it presented so openly in a paper with the names of so many prominent autism researchers attached.
I'm not going to dig into the methods used in the paper because, quite frankly, I have no real understanding of the methods used to arrive at the result and so I don't have an opinion on whether the results fit the data. If you want a good summary of the results in the paper, I suggest you read the write up over at Questioning Answers.
What I am going to point out is the excellent background section at the start of the paper. The paper is open access, so I if you are interested in the genetic of autism I suggest you read at least that section. I also wanted to point out two little bits from this section -
Beliefs about the genetic architecture of autism spectrum disorders (ASD) have changed dramatically over the past few decades. Early twin studies produced heritability estimates approaching 90% and, while no specific risk loci were known at the time, it was believed that liability was conferred by a handful of genes of large effect. Later, data on the distribution of ASD within families, together with results from linkage analyses, were interpreted to mean that liability arose from many genes. Recent work has definitively demonstrated the substantial contribution of de novo variation. Indeed multiple studies of rare single nucleotide and copy number variants (CNVs) have suggested that 15% or more of liability traces to de novo mutation, effects that are genetic but not inherited.and
[D]espite a near-consensus that common and transmitted variation must confer liability, multiple genome-wide association studies have so far not revealed replicable common polymorphisms associated with ASD, and studies of rare structural and sequence mutations have largely failed to account for the anticipated risk associated with transmitted variation.I may be reading too much into these statements, but it almost seems like the paper is admitting that the assumption that autism is primarily an inherited genetic disorder is flawed. Of course, the data in the paper tries to save the idea by suggesting that the genetic risk for autism comes from tens, hundreds, or thousands of small inherited mutations which, when acting together, give a greater risk for autism.
And who knows, that idea may actually be true. Maybe the genetic side of autism does in fact come from many small mutations acting together. But here is the thing about science - it is all about the evidence. An estimate from applying some fancy algorithm to an already over analyzed genetic data set doesn't tell us anything new.
Despite a "near-consensus" that there have to be common genetic mutations that are passed from parent to child that increase the risk of autism, the fact is that after years upon years of looking no one has found them. All that has been found are some relatively rare inherited conditions and a bunch of non-inherited mutations that, when taken together, make up the minority of cases of autism.
In fact, I would say that the lack of findings despite the efforts to date make a pretty convincing case that such common mutations do not exist, the evidence of twin and other studies notwithstanding. Maybe it is time to start looking in more promising areas such as epigenetics or the biology of autism?
Klei L, Sanders SJ, Murtha MT, Hus V, Lowe JK, Willsey AJ, Moreno-De-Luca D, Yu TW, Fombonne E, Geschwind D, Grice DE, Ledbetter DH, Lord C, Mane SM, Lese Martin C, Martin DM, Morrow EM, Walsh CA, Melhem NM, Chaste P, Sutcliffe JS, State MW, Cook EH Jr, Roeder K, Devlin B. Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism. 2012 Oct 15;3(1):9. [Epub ahead of print] PubMed PMID: 23067556 DOI : 10.1186/2040-2392-3-9