title: On individual genome-wide association studies and their meta-analysis.
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.
authors.affiliation: Center of System Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai, 200093, People's Republic of China, pyf0419@gmail.com.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Pei
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D005787:Gene Frequency; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008962:Models, Theoretical; D010641:Phenotype; D018401:Sample Size