The SLEGEN Process

Throughout the three-year study, the SLEGEN scientists shared a common purpose, a methodical approach and a collaborative spirit.

Quality Control

Working in tandem, researchers started by making sure all project data met strict quality-control guidelines:

• Some verified the accuracy of the genotype data of the 317,503 single nucleotide polymorphisms (SNPs) to be studied.
• Others confirmed that participants met the stringent American College of Rheumatology (ACR) diagnostic definition for lupus.
• A third group merged out-of-study control samples with the SLEGEN data to ensure consistent genotype analysis across all laboratories involved in the project.

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.

Data Analysis

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?

Findings

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.

What this means for people with lupus:

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.

Slegen at a Glance

• The International SLE Genetics (SLEGEN) Consortium is an international, collaborative effort to identify the underlying genetic causes of lupus.
• More than 100 scientists from around the world contributed to the project, which represents decades of research.
• They scanned the entire genome for more than 317,000 SNPs with the goal of identifying SNPs linked to lupus.
• After three years, four genetic candidates showed a strong linkage to lupus.
• The SLEGEN program opens the door for further funding of targeted grants.
• Future research will target specific genetic pathways as scientists strive to develop new treatments, tests and, ultimately, a cure.