eLD: entropy-based linkage disequilibrium index between multiallelic sites.

Quantification of linkage disequilibrium (LD) is a critical step in studies investigating human genome variations. Commonly used LD indices such as r 2 handle LD of biallelic variants for two sites. As shown in a previously introduced LD index of ε , normalized entropy difference of the haplotype frequency between LD and linkage equilibrium (LE) could be utilized to estimate LD of biallelic variants for multiple sites. Here, we developed eLD ( e ntropy-based L inkage D isequilibrium index between multiallelic sites) as publicly available software to calculate ε of multiallelic variants for two sites. Application of eLD could dissect complex LD structures among multiple HLA genes (e.g., strong LD among HLA-DRB1 , HLA-DQA1 , and HLA-DQB1 in East Asians). Use of eLD is not restricted to haplotype-based LD; it is also applicable to genotype-based LD. Therefore, eLD enables estimation of trans -regional LD of SNP genotypes at two unlinked loci, such as the nonlinear LD between functional missense variants of ADH1B (rs1229984 [Arg47His]) and ALDH2 (rs671 [Glu504Lys]).