Case-control genetic association studies in gastrointestinal disease: review and recommendations

As our knowledge of genetic variation grows, our ability to use this information to unravel the mysteries of human disease expands. Identification of genes and inexpensive methods to sequence them has resulted in a rising interest in evaluating specific variants and whether they may result in clinical manifestations or symptoms. Genetic variants include restriction fragment length polymorphisms, variable number tandem repeats, DNA microsatellites, and single nucleotide polymorphisms. Using these variants, genetic association studies, also referred to as candidate gene association or genotype-disease association studies are being performed by clinical and basic researchers alike. They are relatively easy to perform, but as a result of their deceivingly simple design, can be conducted or interpreted poorly. A positive association between a genotype and a GI disease of interest may be because the genotype causes (or increases susceptibility to) the disease, but may also be the result of the genotype being in linkage disequilibrium with the actual disease susceptibility gene, or be a false positive due to chance or bias in study design. An excellent understanding of the genetic and methodological issues surrounding these studies is therefore essential. We provide an overview of terminology and provide insight into the complexities underlying these studies. Recommendations for reporting the results of a genetic association study are provided to assist with study planning and manuscript preparation.