- In genetic studies, one potential cause of spurious associations is differences between cases and controls in ethnicity, a situation termed population stratification.
- Was measurement of the genetic variants unbiased and accurate?
- Methods for determining DNA sequence variation are not perfect and may have some measurement error.
- Do the genotype proportions observe Hardy-Weinberg equilibrium?
- Have the investigators adjusted their inferences for multiple comparisons?
I have several others to add to this list, but HUGENet covers most of them. What is HUGENet? It is the Human Genome Epidemiology Network and it is a "global collaboration of individuals & organizations committed to the assessment of the impact of human genome variation on population health & how genetic information can be used to improve health & prevent disease."
In essence this voluntary set of collaborators evaluates epidemiologically, NOT CLINICALLY, but epidemiologically whether a GWAS or other Genome study is valid. PLOS reviews thet workings of HUGENet in a nice article.
This is an important network to have.
In addition, EGAPP (Evaluation of Genomic Applications in Practice and Prevention) evaluates the validity and applicability of these results if they are attempted to be turned into clinical practice. This too is a consortium of physicians and scientists evaluating such tools. Genetics in Medicine has a nice article about the methods of EGAPP too.
It is important to note that these are not "in house" services. Why do I say that? Well it is a little cloudy if a company such as Navigenics or deCode is telling you that their tests are clinically valid......Why? Well, they are selling the tests. Doesn't that make you stop and think?
How does Navigenics review studies for clinical applicability? They have posted on it. In essence they require at least 250 cases and controls and have a limited requirement for independent replications.....unlike HUGENet.
Thus the quandary with "in house" statistical analysis for scientific validity OR clinical utility.
The Sherpa Says: If you want to know the skinny on any of these studies, you need look no further than EGAPP or HUGENet....rather than trying to make sense of it through your 23andME account or tursting deCode or Navigenics to provide "unbiased" evaluations.....