Genome-wide Association Study for Pancreatic Cancer in Jewish Subjects

Figure 2. Manhattan plot of SNP P-values from the full-Jewish GWAS. The Y-axis shows the negative base ten logarithm of the P-values and the X-axis shows the chromosomes. The genome-wide significance threshold, P<10-7.3 (i.e. P<5x10-8) is shown in red.

Jews have been found to have a higher risk of pancreatic cancer compared to non-Jewish whites. Our research explored a genetic basis for this higher risk. We examined the existing significant loci from the large white-European Pancreatic Cancer Cohort and Case-Control Consortium/Pancreatic Cancer Case-Control Consortium (PanScan/PanC4) genome-wide association studies (GWASes) and performed the first GWAS of pancreatic cancer in the higher-risk Jewish population.  Among Jewish subjects, we found a novel genome-wide significant association with pancreatic cancer on chromosome 19p12 and a suggestive relatively independent association on 19p13.3, which may explain much of the increased risk of pancreatic cancer in the Jewish population compared to the non-Jewish white European population. Our findings are published in Cancer Epidemiology, Biomarkers & Prevention and Human Genetics1,2.

The Yale Center for Research Computing (YCRC) supported our analyses, and the Yale high performance computing (HPC) cluster enabled us to analyze and store large amounts genetic data. On the HPC cluster, we were able to genetically identify Jewish subjects from over 50,000 white-European subjects, impute missing genotypes between different genotyping platforms, and run a pancreatic cancer GWAS in Jewish subjects. If our findings are further validated, testing of these loci should be considered for Jewish individuals with family histories of pancreatic cancer not otherwise explained by known predisposition mutations.
 
References

  1. Streicher SA, Klein AP, Olson SH, Amundadottir LT, DeWan AT, Zhao H, Risch HA. Impact of sixteen established pancreatic cancer susceptibility Loci in American Jews. Cancer Epidemiol Biomarkers Prev 2017;26:1540-48.
  2. Streicher SA, Klein AP, Olson SH, Kurtz RC, Amundadottir LT, DeWan AT, Zhao H, Risch HA. A pooled genome-wide association study identifies pancreatic cancer susceptibility loci on chromosome 19p12 and 19p13.3 in the full-Jewish population. Hum Genet 2020;epub ahead of print.