Omni1m quad platform

Genotyping of DNA from buffy coat or whole-blood samples was performed using the Illumina Omni1M Quad platform (San Diego, CA) in accordance with standard quality-control procedures.^{15 (link),16 (link)} The annotations were based on version H of the Illumina product files and corresponded to the Genome Reference Consortium GRCh37 release. For quality control, genotyped single-nucleotide polymorphisms (SNPs) or samples with a call rate less than 95% were excluded. Based on control participants, SNPs with Hardy-Weinberg equilibrium P values less than 10⁻⁴ or minor allele frequency less than 0.01 also were excluded. Imputation was conducted at the study level, based on SHAPE1T2/1MPUTE2 using 1000 Genomes Phase 3 integrated variant set release in NCB1 build 37 (hg19) coordinates.^{17 (link)} Postimputation quality control excluded SNPs with an 1MPUTE2 information score less than 0.8, call rate less than 95%, Hardy-Weinberg equilibrium P value less than 10⁻⁴ based on control participants, or minor allele frequency less than 0.01 in control participants.

The BEACON GWAS included men and women diagnosed with EA or BE, and control participants pooled from 14 individual studies conducted in Western Europe, Australia, and North America over the past 20 years. Detailed study population characteristics and genotyping protocols have been published [24 (link)]. The current analysis employed a pooled dataset [30 (link)] that included participants of European ancestry from the BEACON GWAS, additional BE and EA patients from the UK Barrett’s Esophagus Gene Study and the UK Stomach and Oesophageal Cancer Study (SOCS), respectively [24 (link)], and additional control participants from a hospital-based case-control study of melanoma conducted at the MD Anderson Cancer Center (Houston, TX) [31 (link)]. Genotyping of buffy coat or whole blood DNA from all participants was conducted using the Illumina Omni1M Quad platform, in accordance with standard quality control procedures [32 (link)]. All participants gave written informed consent, and this project was approved by the ethics review board of the Fred Hutchinson Cancer Research Center. We selected all unrelated participants with <2% missing genotyping calls; thus the final study sample included 2,515 EA cases, 3,295 BE cases, and 3,207 controls. Three control participants were excluded from analyses involving BE cases, because of familial relation to cases.