CLD: Rare-variant linkage disequilibrium between genomic regions identifies novel genomic interactions.

ABSTRACT: Linkage disequilibrium (LD) is a fundamental concept in genetics; critical for studying genetic associations and molecular evolution. However, LD measurements are only reliable for common genetic variants, leaving low-frequency variants unanalyzed. In this work, we introduce cumulative LD (cLD), a stable statistic that captures the rare-variant LD between genetic regions, which reflects more biological interactions between variants, in addition to lack of recombination. We derived the theoretical variance of cLD using delta methods to demonstrate its higher stability than LD for rare variants. This property is also verified by bootstrapped simulations using real data. In application, we find cLD reveals an increased genetic association between genes in 3D chromatin interactions, a phenomen

SUBMITTER: Wang D 

PROVIDER: S-EPMC10758262 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature