We found that 73% of SVs with >1% VAF and 68% of rarer SVs (VAF > 0.1%) are in linkage disequilibrium (LD) with nearby single nucleotide polymorphisms (SNPs) (r2 > 0.6); however, the proportion of variants in LD highly depends on the SV class (Fig. 1e, Extended Data Fig. 4). For example, only 44% of all biallelic duplications with VAF > 0.1% were in LD with a nearby SNP (r2 > 0.6), in agreement with previous findings10,25,26. Notably, we observed a striking depletion of biallelic duplications amongst common SVs (P < 2 × 10−16, Kolmogorov–Smirnov test; Extended Data Fig. 5) with most common duplications classified as multi-allelic SVs (that is, mCNVs). This behaviour suggests extensive recurrence of SVs at duplication sites consistent with what was recently observed in a smaller cohort of 849 individuals27. These LD characteristics suggest duplications are currently under-ascertained for disease associations using tag-SNP-based approaches.
