The chapter is divided into two principal sections: (1) a summary of factors that affect the quality of individual array results; and (2) a discussion of experimental design features and replication criteria that enable researchers to gain confidence in their findings.
With more stringent replication criteria, that requires LO D = 3 and maximum QTL LOD position in the 30–40 cM interval, 929 (59%) eQTL replicate.
The replication criteria used in our study were particularly strict and required a significant p-value in both, the family-based and the case-control association test in two different populations.
While only these six SNPs were found to be nominally significant in both, the TDT and the case-control analysis, and therefore fulfilled the formal replication criteria, 47 SNPs were significant in only one test, including two more SNPs in the 5p13.1 region (#79, #105), one in NELL1 (#116), and one in the IBD5 region (#191).
Three of these 49 loci were already known to be associated with AMD and the SNPs meeting our replication criteria (Table 1) from the remaining 46 loci were genotyped in a second, independent group of subjects with and without AMD from the Mayo Clinic.
Strict replication criteria were used in the single-marker analyses (Konig 2011).
Some of the CpGs that we identified with the recursive RF but that did not meet our replication criteria may in fact be biologically relevant in atopy.
Therefore, stringent replication criteria are necessary to avoid false positives and to ultimately confirm that a certain genetic variant confers susceptibility to disease [ 4].
In order to gauge the robustness of the above findings in the absence of the gene-length bias that may have been introduced with the relaxed replication criteria, the CNS-specific IPA analysis was also performed on gene lists constructed on the basis of more stringent replication criteria.
This finding, which was unique to gC, also survived the FDR multiple-testing correction at the more conservative 0.05 threshold and the application of more stringent replication criteria for the construction of gene lists.
