Chunk #31 — Reasons to be Concerned about the Published cGxE Literature — The Ingredients of cGxE: The Choice of Genetic and Environmental Variables — The Choice of “G”
For example, the vast majority of the “G” that has been incorporated into cGxE studies consists of a handful of “usual suspect” candidate genes (Munafo, 2006; e.g., SLC6A4 [aka 5-HTT, MAOA, DRD2, COMT]), as discussed above. Often a single genetic marker is genotyped to represent the gene. Genotyping a single marker in a gene does not reflect the state of the science in genetics, which has moved toward more comprehensive approaches to gene finding. It may be appropriate to genotype a single genetic variant when that variant has a known functional impact on the gene, (i.e., it produces an observable alteration in the manner in which the gene encodes the protein product). However, over and above this simple annotation of function, the impact of a candidate polymorphism is very challenging to establish. At its simplest, even when modeling a single variant, the characterization of that variant (or its mode of inheritance) can profoundly impact detection of cGxE. For instance, which allele is assigned as a risk allele, and how many copies of this allele are required to quantify the diathesis,
