Supplementary Material for: Pooling-Based Genome-Wide Association Study Implicates Gamma-Glutamyltransferase 1 (GGT1) Gene in Pancreatic Carcinogenesis

<p><i>Background/Aims:</i> Knowledge regarding genetic factors that influence pancreatic cancer risk is currently limited. To identify novel pancreatic cancer susceptibility loci, we conducted a two-stage genome-wide association study. <i>Methods:</i> The Affymetrix® Genome-Wide Human SNP Array 6.0 and DNA pooling were used in the screening stage. Twenty-six single-nucleotide polymorphisms (SNPs) were selected for follow-up. These 26 lead SNPs and additionally selected tagSNPs for the regions around the lead SNPs were evaluated by individual genotyping of the pooling population and an independent validation population. <i>Results:</i> Of the lead SNPs, the strongest association was found with rs4820599 located in the γ-glutamyltransferase 1 (<i>GGT1)</i> gene. This SNP was significantly associated with pancreatic cancer risk in the validation population and the combined dataset (p<sub>allele-based</sub> = 0.019 and p<sub>allele-based</sub> = 0.003, respectively). Statistically significant associations were also observed with two <i>GGT1</i> tagSNPs: rs2017869 and rs8135987. Lead SNP rs4820599 is in high linkage disequilibrium (LD; pairwise r<sup>2</sup>: 0.69) and tagSNP rs2017869 is in strong LD (pairwise r<sup>2</sup>: 0.96) with SNP rs5751901, which has been reported to be associated with increased GGT1 serum levels. GGT is expressed in the pancreas and plays a key role in glutathione metabolism. <i>Conclusion:</i> Our results suggest that common variation in the <i>GGT1</i> gene may affect the risk of pancreatic cancer.</p>