Genome wide association studies as a methodology for studying complex genetic traits in humans - successes and limitations
Genome Wide Association Studies were first proposed in the mid-1990s as a way to study association between human genetic polymorphisms and complex, multigenic traits. Rather than measure all genetic variation present in each individual, approximately one million Single Nucleotide Polymorphisms (SNPs) are assayed as genetic landmarks, and scored for association with the trait of interest. Based on linkage disequilibrium, genes in close proximity to associated SNP landmarks are potential candidates for further investigation.
This technique is well-suited to identify susceptibility genes that are of intermediate prevalence in the population, with a Mean Allele Frequency of greater than 0.05 (Risch and Merikangas, 1996). Although no such studies of Lyme arthritis severity have been conducted, GWAS has been extensively used to investigate genetic modulators of other inflammatory conditions including rheumatoid arthritis (RA). Thus far, almost fifty susceptibility loci have been identified for RA, accounting for approximately one-half of the total genetic variation expected in populations of European ancestry. Nineteen of these loci have been refined to a single candidate gene association, and the underlying causal polymorphism has been predicted for seven of these loci (Eyre et al., 2012).