A position in the DNA sequence at which there are at least two forms in the population. A genetic variant that is within a region of the genome that codes for a protein (i.e., is in an exon), can be categorised as either synonymous (i.e., both forms code for the same amino acid and the form that might be considered a mutation has no downstream effect on the protein structure that is synthesized) or non- synonymous (i.e., one form (the mutation form) changes the amino acid and protein structure). Synonymous variants can still have robust associations with phenotypes through gene regulation.
The genetic variants used as IVs in MR studies are usually SNPs. However, the term “genetic variant” can refer to other variations within the genome (e.g., chromosome abnormalities, copy number variation, insertions/deletions or other sequence variations). Whilst most genetic variants occur outside coding regions, these are completely valid for MR analyses, even though their function or how they influence the exposure of interest is unknown.
- Wain LV, Armour JA, Tobin MD. Genomic copy number variation, human health, and disease. Lancet 2009;374:340-50.
- Buxton J, Turney J. The Rough Guide to Genes & Cloning 2007.