Meta-Analysis of Rare Variants

  • Ioanna Tachmazidou
  • Eleftheria Zeggini


Meta-analysis is the use of statistical methods to synthesize results of individual studies examining the same trait. A genome-wide meta-analysis primarily serves the purpose of combining data to increase power to obtain statistical evidence of association between disease and a single variant that would have otherwise escaped detection, for example because of its small effect size. Furthermore, in the era ofwhole-exome and whole-genome sequencing, aggregate tests that combine information from low frequency/rare variants within a region are typically used to test association of a gene or other chromosomal unit with the trait of interest, as single-point analysis of variants tends to have low power for variants at the low end of the MAF spectrum. Here, we discuss key principles and practical considerations when conducting meta-analysis of single-point and aggregate tests in the presence or absence of modest levels of heterogeneity and across a range of different allelic architectures.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Wellcome Trust Sanger InstituteHinxton, CambridgeUK

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