TOP-LD

TOP-LD provides linkage disequilibrium (LD) estimates derived from high-coverage whole-genome sequence (WGS) data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program to support genetic association and population-genetic analyses.

Key Features:

• Enhanced genetic variation representation: Leverages high-coverage (~30×) WGS from 15,578 TOPMed individuals to improve detection of rare variants and population-specific variation.
• Expanded variant coverage: Includes LD information for ~150.3 million variants in European samples, 62.2 million in African samples, and 36.7 million in East Asian samples, representing a 2.6- to 9.1-fold increase over HaploReg 4.0 or LDlink (1000 Genomes Project–based) coverage.
• Inclusion of structural variants: Incorporates tens of thousands of structural variants (SVs) into LD estimates to broaden the range of variant types analyzed.

Scientific Applications:

• Fine-mapping: Enables fine-mapping of genetic associations, exemplified by analysis at the GGT1 locus for gamma-glutamyltransferase levels in African-ancestry participants from the UK Biobank.
• Summary-statistics and population genetics analyses: Provides LD estimates for use with summary-statistic methods and population-genetic studies across diverse ancestries.

Methodology:

The methodology infers linkage disequilibrium from high-coverage (~30×) WGS data generated by the NHLBI Trans-Omics for Precision Medicine (TOPMed) program.