Key result
A new gene-based association test identified the PHF19 gene region (p=9.61x10^-7) associated with rheumatoid arthritis that was missed by standard SNP-based testing, demonstrating complementary utility.
Gene-based and SNP-based association tests are complementary strategies in GWAS, as they can identify different genetic loci associated with complex diseases.
Gene-based tests may reveal RA loci missed by SNPs; leaves open clinical translation pending replication and functional validation.
Genome-wide association studies are widely used today to discover genetic factors that modify the risk of complex diseases. Usually, these methods work in a SNP-by-SNP fashion. We present a gene-based test that can be applied in the context of genome-wide association studies. We compare both strategies, SNP-based and gene-based, in a sample of cases and controls for rheumatoid arthritis.We obtained different results using each strategy. The SNP-based test found the PTPN22 gene while the gene-based test found the PHF19-TRAF1-C5 region. That suggests that no single strategy performs better than another in all cases and that a certain underlying genetic architecture can be delineated more easily with one strategy rather than with another.
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Buil et al. (2009) studied Rheumatoid arthritis (n=2,062). Gene-based association test vs. SNP-based association test was evaluated on Identification of genetic loci associated with rheumatoid arthritis. A new gene-based association test identified the PHF19 gene region (p=9.61x10^-7) associated with rheumatoid arthritis that was missed by standard SNP-based testing, demonstrating complementary utility.
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