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Table 2 Methods, tools, literature reviews and resources*

From: Trans-ethnic genome-wide association studies: advantages and challenges of mapping in diverse populations

Method or advance Advances and limitations or main findings References
MANTRA transethnic meta-analysis software Replication of primary signal in WA population and fine-mapping of second independent signal showing positive selection in WA, EA and EUR cohorts. MANTRA is available as a suite of executables on request from the author [58]. Major limitation in that it cannot estimate a joint effect size even for the combined meta-analysis MANTRA [58]; applications: adiposity loci [59]; quantification of serum protein [14]; T2D [33]
RE-HE random-effects method RE and FE models in the context of a meta-analysis with significant heterogeneity have low power. By relaxing overly conservative parameters in RE analysis algorithms, RE-HE provides more power in the presence of inter-study effect heterogeneity. Metasoft is available as a package [114]; it provides a joint effect size estimate, but it is the same as the RE estimate RE-HE algorithm [56]; applications: endometriosis [115]; bipolar disorder [18]; multi-tissue eQTLs [116]
Review on replicability of transethnic association signals Comprehensive review of literature across 28 diseases in EA and EUR populations demonstrating high replicability, sharing of disease alleles and good correlation of effect sizes [43]
Review on power gains in meta-analytical approaches Simulation-based analysis demonstrating that a multi-ethnic study design provides non-trivial power gains, especially when AFR populations are used to examine low frequency alleles (MAF <5%) [117]
Comparative analysis of FE, RE, RE-HE and MANTRA as a method for GWAS meta-analysis Results show that both RE-HE and MANTRA are computationally efficient and robust methods in accounting for effect size heterogeneity while providing a boost in power when compared with traditional meta-analysis methods. Results are provided for both simulations and application to T2D datasets [57]
Modified RE-HE for joint analysis of resequencing data for rare variant gene-based analysis Extension of RE-HE to provide a more powerful (than traditional RE) method to perform rare-variant burden testing in a heterogeneous resequencing study sample [44]
  1. *Summary of innovative methods, applications and literature reviews as highlighted in the main text. We summarize the methodological advances, including those for meta-analysis, any significant or notable limitations, and for reviews. Abbreviations: AFR, African; ALL, acute lymphoblastic leukemia; EA, East Asian; eQTL, expression quantitative trait locus; EUR, European; FE, fixed effects; GWAS, genome-wide association study; LD, linkage disequilibrium; MAF, minor allele frequency; RE, random effects; RE-HE, alternate random effects; T2D, type 2 diabetes; WA, West African.