An evaluation of different meta-analysis approaches in the presence of allelic heterogeneity

Jennifer Asimit, Aaron Day-Williams, Lina Zgaga, Igor Rudan, Vesna Boraska, Eleftheria Zeggini

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Meta-analysis has proven a useful tool in genetic association studies. Allelic heterogeneity can arise from ethnic background differences across populations being meta-analyzed (for example, in search of common frequency variants through genome-wide association studies), and through the presence of multiple low frequency and rare associated variants in the same functional unit of interest (for example, within a gene or a regulatory region). The latter challenge will be increasingly relevant in whole-genome and whole-exome sequencing studies investigating association with complex traits. Here, we evaluate the performance of different approaches to meta-analysis in the presence of allelic heterogeneity. We simulate allelic heterogeneity scenarios in three populations and examine the performance of current approaches to the analysis of these data. We show that current approaches can detect only a small fraction of common frequency causal variants. We also find that for low-frequency variants with large effects (odds ratios 2-3), single-point tests have high power, but also high false-positive rates. P-value based meta-analysis of summary results from allele-matching locus-wide tests outperforms collapsing approaches. We conclude that current strategies for the combination of genetic association data in the presence of allelic heterogeneity are insufficiently powered.
Original languageEnglish
Pages (from-to)709-712
Number of pages4
JournalEuropean Journal of Human Genetics
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Dive into the research topics of 'An evaluation of different meta-analysis approaches in the presence of allelic heterogeneity'. Together they form a unique fingerprint.

Cite this