Neonatal blood transcriptomics reveal expression signatures of adhd risk

Attention-deficit / hyperactivity disorder (ADHD) is a neurodevelopmental disorder with well established associations with pregnancy outcomes. We hypothesised that transcriptomic profiles at birth capture in-utero exposures in addition to genetic factors that are responsible for the onset of ADHD symptoms later in life. To test our hypothesis, we sequenced RNA from blood which had been kept in storage by being transferred to filter paper, dried, and stored at -20°C for up to 39 years. We sequenced RNA from 305 twin-pairs, 38 of whom have a concordant ADHD diagnosis, and 120 of whom have a discordant ADHD diagnosis, according to data from Danish registers. After ensuring that data obtained from DBS is of sufficient quality to perform downstream analysis, we tested for differential expression between cases and controls, and performed pathway analysis on genes we found to be significantly differentially expressed. We found there is no loss of resolution in RNA-seq data obtained from DBS samples, and that we can successfully correct for bias due to non-random transcript degradation by using principal components. Genes which were differentially expressed in individuals who developed ADHD were primarily expressed in platelets and cerebellar tissue, and were involved in immune system response, cell-binding, and signalling. By sequencing RNA from decade-old blood, we could successfully establish clear differences in the transcriptomic profiles of individuals diagnosed with ADHD later in life. This potentially paves the way for the discovery of biomarkers present at birth which are indicative of an increased risk of developing ADHD later on in life.