Different biases in meta-analyses of case-control and cohort studies: an example from genomics and precision medicine

Meta-analyses of observational studies reduce the role of chance but also introduce bias because the individual component studies are not randomized. Further, it is plausible that the bias may be different in case-control and cohort studies. We explored these issues in meta-analyses of observational studies of Opioid Use Disorder (OUD).

From a systematic literature review of 152 published meta-analyses, 11 fulfilled the initial inclusion criteria of observational studies of OUD. Of these, 9 were meta-analyses of case-control studies and 2 were meta-analyses of cohort studies but only 4 (3 case-control and 1 cohort) targeted more than one specific chromosomal location.

The meta-analyses of the 3 case-control studies, which included 13 individual studies, identified 12 different single nucleotide polymorphisms on 6 different genes on 5 different chromosomes. None was the same as the gene on Chromosome 15 identified from the meta-analysis of the cohort studies.

These data, from genetic studies, suggest biases are different in meta-analyses of case-control and cohort studies, perhaps due to greater selection bias in case-control studies. These observations have potential importance in the application of meta-analyses to many common and serious diseases, as well as genomics and precision medicine, including OUD.