Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes
Figure 1
Main outlines of the research strategy for identifying cis haplotype effects.
(1): Probes with best haplotype signal (HS) 104-fold smaller than the smallest single-locus signal (SLS) in the discovery study (CTS) were selected for replication in GHS. (2): Probes that had cis htSNPs available in GHS were considered as replicable. (3): Probes for which the global test of cis haplotypic association was significant at the Bonferroni threshold (1.21 10−4) in GHS and the pattern of cis haplotypic association was consistent between CTS and GHS (the same haplotypes with effects in the same direction) were considered as replicated. (4): Cis haplotypic associations were considered as validated when the haplotypic p-value was still significant at the Bonferroni threshold (1.21 10−4) after adjusting for the best (genotyped or imputed) SNP identified in single-locus association analysis in GHS. (5): Nested likelihood ratio tests and conditional haplotype analyses were used to check whether validated haplotype effects could be compatible with the additive effects of multiple SNPs (see Methods). (6): cis Haplotype eQTLs overlapping with disease-associated loci obtained from the Genome-Wide Association Studies catalog (Hindorff et al. 2009) [23]. htSNPs: haplotype tagging SNPs.