Synonyms: Colocalization
The phenomenon whereby genetic factors at a particular locus are shared between two or more traits (not to be confused with declaring the exact causal variant). Tests for genetic colocalization try to separate between two scenarios: (i) there is a causal variant for trait A that is distinct from the causal variant for trait B, whilst being at the same locus, and (ii) the causal variant for trait A and trait B are shared. A variety of algorithms exist for distinguishing between these scenarios, typically by looking for concordance of effects across all single nucleotide polymorphisms (SNPs) at the locus at both traits.
Genetic colocalization of a locus between two traits is necessary but not sufficient for a causal relationship, and it can be thought of an MR analysis performed with a single SNP but with an added sensitivity analysis where the possibility that there are two distinct causal variants in the same region is being ruled out. The approach is regularly used to infer putative causal relationships between ‘omic variables and complex traits. Often an assumption of these algorithms is that there is only one causal variant in the region, which may not be appropriate.
References
- Richardson TG, Zheng J, Davey Smith G, et al. Mendelian Randomization Analysis Identifies CpG Sites as Putative Mediators for Genetic Influences on Cardiovascular Disease Risk. The American Journal of Human Genetics 2017; 101: 590-602.
- Giambartolomei C, Vukcevic D, Schadt EE, et al. Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics. PLOS Genetics 2014; 10: e1004383.
- Barbeira AN, Dickinson SP, Bonazzola R, et al. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics. Nature Communications 2018; 9: 1825.