Fig. 4: Integrative model of genetic influences on autism at 16p.

a, On the x axis, the association t-statistics from the all sample meta-analyses of 16p PGS and 16p gene expression; on the y axis, the association t-statistics from the 16p11.2 in vitro deletion analysis. The shaded region is the 95% CI. Genes are colored by their location on 16p; telomeric is defined as a gene midpoint <5.2 Mb. A single outlying point has been truncated from the plot for visualization; the untruncated plot is shown in Supplementary Fig. 22. b, Hi-C analysis revealing elevated within-region chromatin interaction at 16p. Each point represents a 33-Mb partition, with 16p colored blue. Both axes are in units of residual z-score, where the residual is from a linear model regressing out segmental duplication content and gene count from the mean within-region Hi-C contact value (Methods). The x axis is a dataset of LCLs, whereas the y axis is a dataset of midgestational cortical plate. c, Hi-C analysis revealing elevated contact between the 16p11.2 locus and the 5.2-Mb gene-dense telomeric region of 16p in midgestational cortical plate. The triangle depicts the 16p contact matrix: the blue shaded region denotes contacts between the 16p11.2 locus (29.5–30.2 Mb) and the 0- to 5.2-Mb telomeric region (n = 291 100-kb × 100-kb contacts), whereas the red shaded region is the distance between matched controls (n = 1,808 100-kb × 100-kb contacts). The inset shows the distribution of contact values for 16p11.2–telomeric versus control contacts. The P value is from a two-sided, two-sample Student’s t-test. The lower whisker, lower hinge, center, upper hinge and upper whisker correspond to (lower hinge − 1.5× interquartile range (IQR)) and the 25th percentile, median, 75th percentile, and (upper hinge + 1.5× IQR), respectively. d, A model of genetic influences on autism at 16p. Two independent genetic influences on autism—the 16p11.2 deletion and polygenic variation at 16p—are located in a region of elevated 16p chromatin interaction and enriched in brain-specific expression and are associated with coordinated decreased gene expression at 16p.