<unk> es have several issues and limitations that can be taken care of through proper quality control and study setup. Lack of well defined case and control groups, insufficient sample size, control for multiple testing and control for population stratification are common problems. Particularly the statistical issue of multiple testing wherein it has been noted that "the GWA approach can be problematic because the massive number of statistical tests performed presents an unprecedented potential for false-positive results". Ignoring these correctible issues has been cited as contributing to a general sense of problems with the GWA methodology. In addition to easily correctible problems such as these, some more subtle but important issues have surfaced. A high-profile<unk>  that investigated individuals with very long life spans to identify SNPs associated with longevity is an example of this. The publication came under scrutiny because of a discrepancy between the type of genotyping array in the case and control group, which caused several SNPs to be falsely highlighted as associated with longevity. The study was subsequently retracted, but a modified manuscript was later published. In addition to these preventable issues,<unk> es have attracted more fundamental criticism, mainly because of their assumption that common genetic variation plays a large role in explaining the heritable variation of common disease. Indeed, it has been estimated that for most conditions the SNP heritability attributable to common SNPs is <0.05. This aspect of<unk> es has attracted the criticism that, although it could not have been known prospectively,<unk> es were ultimately not worth the expenditure.<unk> es also face criticism that the broad variation of individual responses or compensatory mechanisms to a disease state cancel out and mask potential genes or causal variants associated with the disease. Additionally,<unk> es identify candidate risk variants for the population from which their analysis is performed, and with most<unk> es stemming from European databases, there is a lack of translation of the identified risk variants to other non-European populations. Alternative strategies suggested involve linkage analysis. More recently, the rapidly decreasing price of complete<unk>  sequencing have also provided a realistic alternative to genotyping array-based<unk> es. It can be discussed if the use of this new technique is still referred to as a<unk> , but high-throughput sequencing does have potential to side-step some of the shortcomings of non-sequencing GWA.
Genome-wide association study
Environment-wide association study
Risk panel
Genetic epidemiology
Molecular risk assessment
MIDAS Trial
Subgroup analysis
MOMS Trial