Patterns of linkage disequilibrium in different populations: implications and opportunities for lipid-associated loci identified from genome-wide association studies

Abstract

Genome-wide association studies across numerous populations have uncovered a remarkable number of loci implicated with lipid-related traits. The association signals at a number of these loci have been successfully replicated across multiple populations, but a fraction failed to be reproduced when tested in other populations. The present review examines the patterns of linkage disequilibrium at these lipid-associated loci and the implications to replication studies, meta-analyses and fine-mapping efforts across multiple populations. The extent of linkage disequilibrium has been well established to differ across populations, particularly between African and non-African groups. A novel strategy has been developed for assessing interpopulation variations in regional patterns of linkage disequilibrium. This approach has been applied to the genomes of populations in public databases, identifying regions where linkage disequilibrium is considerably different, some of which exist in regions associated with phenotypic variation. It has been shown that such diversity in linkage disequilibrium can challenge replication studies and meta-analyses while benefiting the pursuit for the functional variants in fine-mapping studies. The next phases in genome-wide studies aim to reproduce the emerging association signals across different populations and to identify the functional variants directly responsible for these signals. Recent publications are beginning to yield valuable insights into the unique challenges and opportunities presented by both consistent and varying patterns of linkage disequilibrium in these follow-up phases.