From SNP to pathway-based GWAS meta-analysis: do current meta-analysis approaches resolve power and replication in genetic association studies?

Genome-wide association studies (GWAS) have benefited greatly from enhanced high-throughput technology in recent decades. GWAS meta-analysis has become increasingly popular to highlight the genetic architecture of complex traits, informing about the replicability and variability of effect estimations across human ancestries. A wealth of GWAS meta-analysis methodologies have been developed depending on the input data and the outcome information of interest. We present a survey of current approaches from SNP to pathway-based meta-analysis by acknowledging the range of resources and methodologies in the field, and we provide a comprehensive review of different categories of Genome-Wide Meta-analysis methods employed. These methods highlight different levels at which GWAS meta-analysis may be done, including Single Nucleotide Polymorphisms, Genes and Pathways, for which we describe their framework outline. We also discuss the strengths and pitfalls of each approach and make suggestions regarding each of them.