On individual genome-wide association studies and their meta-analysis

Hum Genet. 2014 Mar;133(3):265-79. doi: 10.1007/s00439-013-1366-4. Epub 2013 Oct 11.

Abstract

Individual genome-wide association (GWA) studies and their meta-analyses represent two approaches for identifying genetic loci associated with complex diseases/traits. Inconsistent findings and non-replicability between individual GWA studies and meta-analyses are commonly observed, hence posing the critical question as to how to interpret their respective results properly. In this study, we performed a series of simulation studies to investigate and compare the statistical properties of the two approaches. Our results show that (1) as expected, meta-analysis of larger sample size is more powerful than individual GWA studies under the ideal setting of population homogeneity among individual studies; (2) under the realistic setting of heterogeneity among individual studies, detection of heterogeneity is usually difficult and meta-analysis (even with the random-effects model) may introduce elevated false positive and/or negative rates; (3) despite relatively small sample size, well-designed individual GWA study has the capacity to identify novel loci for complex traits; (4) replicability between meta-analysis and independent individual studies or between independent meta-analyses is limited, and thus inconsistent findings are not unexpected.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Frequency
  • Genetic Loci
  • Genome, Human
  • Genome-Wide Association Study*
  • Humans
  • Models, Theoretical*
  • Phenotype
  • Sample Size