Second, there was residual population stratification between the TS cases from the Central Valley of Costa Rica (CVCR) and control samples from Antioquia, Colombia (ANT). Although initially thought to have arisen from common founders22, recent studies suggest that these populations have slight differences in Native American ancestry (A. Ruiz-Linares, N. Freimer, personal communication). Though the resulting λGC of 1.04 in the CVCR/ANT subpopulation analysis is relatively small and thus is likely not to introduce significant bias in a meta-analysis, we chose to reserve these non-European samples for a secondary analysis to provide supportive evidence to individual candidate susceptibility loci. While we did not find significant evidence for a consistent direction of effect between the top signals in the primary European ancestry meta-analysis and those in the CVCR/ANT subpopulation analysis, it is important to note that the CVCR/ANT samples are an admixed population with a significant proportion of non-European ancestry47, and thus do not represent a true replication sample for the European ancestry meta-analysis.
