Fig. 3: RERs are correlated with local recombination rates.
From: Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD
A Density curve for risk-enriched regions (RERs) (“RER”, red), and genes with the highest recombination rate (“Top”, blue, generated from HapMap). The overall recombination rates from HapMap project74 are indicated with a gray smooth line (“HapMap”). The red dots correspond to the top five SNPs identified in a Chr-X-wide association study for loci contributing to the female protective effect86. B Top panel RER genes (red) tend to have high rates of recombination compared to all Chr X non-PAR genes (gray). However, the RER genes only partially overlap the distribution of the top 149 genes based on recombination rate (blue). Bottom panel, Venn diagram depicting the overlap between the 149 genes contained within RERs and the 149 genes with the highest recombination rate. These two gene sets significantly overlap (permutation test with 100,000 iterations), but most of the risk for rare transmitted damaging variants resides within RER genes (one-sided Fisher’s exact tests). C We compared the linear regression models for per gene counts of rare variants occurring across all of Chr X with the formula #ssc_pro.Dam ~ #ssc_sib.Dam + log(recombination rate) (x-axis) and #ssc_pro.Dam ~ #ssc_sib.Dam (y-axis). We transformed the recombination rate to a log scale in order to make its distribution more normal. We then performed F-tests to determine whether log(recombination rate) is a significant covariate. There is no significant difference between the two models (F = 0.253, P = 0.62), suggesting that recombination rate is not a significant predictor of the per gene count of rare damaging variants in probands Chr-X-wide. OR odds ratio. See also Supplementary Fig. 6.
