Chunk #102 — III. Selected Methodological Issues — C. Analyses — 1. Achieving significant genome wide association in single samples vs seeking replication and generalization in multiple samples
As the expected effect of each locus falls from the large effects characteristic of oligogenic influences to the small effects that characterize polygenic influences, however, the sample sizes needed to generate p values in these ranges provide a daunting problem. Costs of individually genotyping such large samples become limiting in all but the best-supported enterprises [144]. The risks of introducing occult heterogeneities increase when subsamples are collected at a variety of distinct sites [126]. As more occult heterogeneities are included as disease and control samples need to be assembled from more and more diverse sources to achieve sufficient “n”, more and more of the results obtained may well represent “false positives” based on such occult sample heterogeneity for genetic background or for heritable traits that are not (nominally) being studied.
