Even with the difficulty of replication notwithstanding, variants with relatively large effects may be identified and replicated in powerful GWA studies [11].
Hence the difficulty of replication.
It also lists methodological challenges researchers can encounter when conducting field experiments, including failure to treat, selective attrition, spillover, difficulty of replication, and black box causality, and discusses available solutions.
Although the number of GWASs has grown dramatically during the last five years [ 36, 37], GWASs have several limitations, such as small sample size, dependence on minor allele frequency and genetic effects, stringent statistical significance, and the difficulty of replication across studies [ 38].
Another factor that may contribute to the difficulty of replication in this field is the possibility that the s allele actually increases sensitivity to the environment in a more general way so that adverse environments will lead to bad outcomes, while positive and supportive environments will lead to benefits.
The reasons may be found in a complex set of unrelated problems of which difficulties in replication of low-dose stimulatory responses resulting from poor study designs, greater societal interest in high-dose effects, linking of the concept of hormesis to the practice of homeopathy, and perhaps most crucially a complete lack of strong leadership to advocate its acceptance in the right circles.
Overall, the data presented in this paper suggest that NBSp70 fibroblasts undergo a form of premature senescence, possibly as a result of difficulties in the replication of telomeres, and this is transduced via the p38/MK2-signalling pathway.
may explain replication difficulties of effects of bilingual cognitive advantages (e.g., [ 18]; for a recent review, see [ 5]).
Also, the locus heterogeneity, which implies that alleles at different loci target the same diseases in different individuals, would increase difficulty in replication of association of a single marker [ 1].
