Chunk #100 — III. Selected Methodological Issues — C. Analyses — 1. Achieving significant genome wide association in single samples vs seeking replication and generalization in multiple samples
There is no clearcut consensus about any single method that will produce only true results from any single sample. One approach to concerns about the large numbers of comparisons that are key components of GWA focuses on achieving “genome wide” significance in single samples. Single samples that demonstrate genome wide significance in this way must contain single SNPs whose association displays a striking nominal p value, often in the neighborhood of ca 10−8 [133, 134]. Such results may be the most likely to be published in prominent journals. However, in most studies with findings of this statistical magnitude, effects of variants at a single locus are sufficiently large that linkage studies also provided significant evidence at the same chromosomal locus [135, 136]. For “oligogenic” contributions to common, complex disorders, seeking association with “genome wide” significance in single samples thus provides a reasonable approach. When there is a large effect of a single gene, a number of corrections for multiple comparisons can be applied without creating many false negatives. Bonferroni corrections for multiple comparisons are advocated by some investigators, though they
