Throughout the three-year study, the SLEGEN scientists shared a common purpose, a methodical approach and a collaborative spirit.
Working in tandem, researchers started by making sure all project data met strict quality-control guidelines:
Once the data were verified and in a workable form, the researchers began looking at each of the individual SNPs - one at a time across the entire genome.
First, the scientists identified proportional differences in genotypes between known cases of lupus and the control group. When differences were discovered, the SNPs that fell outside of the expected realm of chance were studied for a potential link to lupus.
Researchers then looked at combinations of SNPs that appear next to one another (haplotypes). They studied how the genotype frequencies for specific adjoining SNPs varied between cases and controls.
If statistical evidence supported these frequency differences, the scientists set out to determine where a SNP candidate was located in proximity to a gene and whether or not it occurred in a coding or a regulatory region. SLEGEN researchers compared their findings to published genetic databases in an attempt to provide context for the SNPs in question. Did the SNPs occur in a region associated with the immune system?
At the end of the study, the scientists discovered strong evidence of an association with SNPs in three known genes, one DNA unit not found within any known gene, and evidence linking lupus to nine other genes.
These landmark results begin to tell the story of which genes might be involved in pathways that influence susceptibility to lupus, as well as complications associated with the disease. Ultimately, by understanding how the SNP affects a gene, scientists can develop therapies and improve diagnostic tools - translating the SLEGEN research into care and, one day, a cure.
“In the field of translating research into care and diagnosis of people with lupus and ultimately with getting to the point of cure, the gnome-wide association project is a wonderful foundation - a critical piece of the puzzle.”
- Carl Langefeld, PhD, SLEGEN Co-Director