Extended Data Fig. 9 |. Transcriptomic correlates of atypical connectivity patterns associated with ASD-related behaviors.

To further assess relationships between gene expression with atypical connectivity and behavior in larger useable samples (that is, now including subjects with usable fMRI data who were excluded from primary analyses due to incomplete behavioral assessments) we started with the N = 782 subjects with usable scan data, and split the N_VIQ = 590 subjects with VIQ into VIQ bins (ASD subjects with [N_VIQ>120 = 127] VIQ > = 120, [N_{85≤VIQ≤120} = 383] VIQ 85–120, or [N_VIQ<85 = 80] VIQ < = 85). We also split the N_ADOS-2 = 353 subjects with ADOS-2 assessment into bins by calculating social affect divided by RRB. The social affect > RRB bin (social affect / RRB > 1) had N_SA>RRB = 113 ASD subjects and the RRB > social affect bin (social affect / RRB >1) had N_SA<RRB = 171 ASD subjects; the N_SA=RRB = 69 ASD subjects with SA/RRB = 1 were not included in either ADOS-2 bin. The overlap of subjects between the N_VIQ = 590 subjects with VIQ and N_ADOS-2 = 353 subjects with ADOS-2 was the N_VIQ;ADOS-2 = 299 ASD subjects in the main analysis. We used the same PLS and gene set enrichment procedure as in Fig. 5 (see b,d,f,h,j,l in box) to assess the relationship of these binned subjects’ atypical connectivity with gene expression. Heatmaps of gene set enrichment for each subgroup’s ranked gene weights for (a-b) ASD-related gene sets, (c-d) nonpsychiatric disease-related gene sets, (e-f) psychiatric disorder-related gene sets, (g-h) synaptic signaling gene sets, (i-j) immune signaling gene sets, and (k-l) protein translation gene sets. Color indicates strength of negative log transformed FDR for normalized enrichment score multiplied by sign of gene weight (+1 or −1). The results were consistent with our predictions: gene set enrichments for the low-VIQ bin resembled those for subgroup 2 (featured low Verbal IQ) and enrichments for the high-VIQ bin resembled those for subgroup 1 (featured above-average VIQ). See further description of results in Supplementary Discussion. The P values were calculated and FDR-corrected as in Fig. 5.