Advances in omics technologies have led to the discovery of genetic markers, or single nucleotide polymorphisms (SNPs), that are associated with particular diseases or complex traits. Although there have been significant improvements in the approaches used to analyse associations of SNPs with disease, further optimised and rapid techniques are needed to keep up with the rate of SNP discovery, which has exacerbated the 'missing heritability' problem. Here, we have devised a novel, integrated,

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... ristic-based, hybrid analytical computational pipeline, for rapidly detecting novel or key genetic variants that are associated with diseases or complex traits. Our pipeline is particularly useful in genetic association studies where the genotyped SNP data are highly dimensional, and the complex trait phenotype involved is continuous. In particular, the pipeline is more efficient for investigating small sets of genotyped SNPs defined in high dimensional spaces that may be associated with continuous phenotypes, rather than for the investigation of whole genome variants. The pipeline, which employs a consensus approach based on the random forest, was able to rapidly identify previously unseen key SNPs, that are significantly associated with the platelet response phenotype, which was used as our complex trait case study. Several of these SNPs, such as rs6141803 of COMMD7 and rs41316468 in PKT2B, have independently confirmed associations with cardiovascular diseases (CVDs) according to other unrelated studies, suggesting that our pipeline is robust in identifying key genetic variants. Our new pipeline provides an important step towards addressing the problem of 'missing heritability' through enhanced detection of key genetic variants (SNPs) that are associated with continuous complex traits/disease phenotypes. PLOS ONE | https://doi.org/10.1371/journal.pone.0175957 April 25, 2017 1 / 25 OPEN ACCESS Citation: Salehe BR, Jones CI, Di Fatta G, McGuffin LJ (2017) RAPIDSNPs: A new computational pipeline for rapidly identifying key genetic variants reveals previously unidentified SNPs that are significantly associated with individual platelet responses. PLoS ONE 12(4): e0175957. https://