RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation.

The sample was very small: only 36 samples were analysed for differential expression, and the authors said it was not powered to detect small methylation differences. Blood gene expression was used as a proxy for brain biology, and the link between blood and brain expression is not fully understood. Samples were collected in adolescence, so it is unknown whether the differences reflect early development or consequences of ASC. The study was discovery-focused and used a false discovery rate threshold of 10%, so findings need replication. All samples were of white ethnic origin, so the signatures may not generalise to other populations. The sample contained only two affected females, so sex-specific effects could not be examined. No full blood cell counts were available, so immune findings could relate to cell composition rather than disease biology. The authors did not perform causal inference, so these signatures cannot show that gene expression changes cause ASC.

The funding statement names the Royal Society and the UK Medical Research Council.

Do not read these blood gene differences as a diagnostic test or a treatment target for autism. The study had a small sample, used blood rather than brain tissue, collected expression in adolescence, and did not test whether the genes cause ASC.