Limitations
GWA studies 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. To this end it has been noted "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 GWA study investigating individuals with very long life spans in order to identify SNPs associated with longevity has been mentioned as 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.
In addition to these preventable issues, GWA studies have attracted more fundamental critiscism, mainly because of their assumption that common genetic variation plays a large role in explaining the heritable variation of common disease. This aspect of GWA studies has attracted the criticism that, although it could not have been known prospectively, GWA studies were ultimately not worth the expenditure. Alternative strategies suggested involve linkage analysis. More recently, the rapidly decreasing price of complete genome sequencing have also provided a realistic alternative to genotyping array-based GWA studies. It can be discussed if the use of this new technique will still be referred to as a GWA study, but high-throughput sequencing does have potential to side-step some of the shortcomings of non-sequencing GWA.
Read more about this topic: Genome-wide Association Study
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