We newly genotyped 6,483 cases and 5,488 controls using the Illumina Global Screening Array (GSA), which included two studies (East-GWAS: 4,872 cases and 3,397 controls from Jiangsu province and Shanghai; North-GWAS: 1,611 cases and 2,091 controls from Shandong province, Hebei province and Tianjin). We consecutively recruited histopathologically confirmed gastric cancer cases from hospitals. Cancer-free controls were selected from individuals receiving routine physical examination at hospitals or those participating in community screening for non-communicable diseases. Demographic characteristics of all participants were displayed in Table S1. Onco-GWAS:Histopathologically confirmed gastric cancer cases were consecutively recruited from hospitals in Jiangsu province, China. The cancer-free control subjects were selected from individuals receiving routine physical examination at hospitals or those participating in community screening for non-communicable diseases in Jiangsu province. A total of 1,140 cases and 345 controls were genotyped using the Illumina OncoArray, and 708 controls were genotyped using the Illumina OmniZhongHua chips (Table S1). Detailed study design and genotype calling was provided previously. 1 NJ-GWAS and BJ-GWAS:For the NJ-GWAS and BJ-GWAS, individuals were derived from separate casecontrol studies conducted in Nanjing (565 cases and 1,162 controls) and Beijing (468 cases and 1,123 controls) (Table S1). Individuals were genotyped using the Affymetrix Genome-Wide Human SNP Array (V.6.0), which consisting ~ 900,000 markers. The details of study design and relevant data were reported previously. 2 1.4 SX-GWAS: A total of 1625 gastric cancer cases and 2100 controls were from the Shanxi Upper Gastrointestinal Cancer Genetics Project and the Linxian Nutrition Intervention Trial (Table S1). All participants were genotyped using the Illumina 660W Quad chip. The study was reported elsewhere 3 and the genotype data was downloaded from dbGap (study accession: phs00361.v1.p1). Quality control.The same protocol of quality control procedures on genotyping data was applied for all six GWAS datasets. The genotyped variants were excluded if they had a call rate of <95%, a P value for Hardy-Weinberg Equilibrium (HWE) in controls ≤1.0×10 −6 or a minor allele frequency (MAF) of <1% in controls; and samples were removed if they were with call rates of <95%, outliers (>6 s.d. from the mean) in population stratification analysis and heterozygosity analysis, or duplicated or related individuals (PI_HAT > 0.25).A total of 100,641 samples in the CKB cohort were genotyped with a customized Affymetrix Axiom® CKB array. Samples with call rate < 98% or gender discrepancy, or samples with extreme heterozygosity (F statistic S.D. score <5) were excluded. Variants with call rate <95% were excluded. Variants with call rate ≥ 95% and < 98%, or deviation from the expected frequency as observed in the 1000 Genomes project (the Phase III integrated variant set release, 504 East Asians), or deviation from Hardy-Weinberg disequil...

Background and Aim Helicobacter pylori (H. pylori) infection rates have been changing with different populations and geographic areas. We systematically evaluated the longitudinal trends in H. pylori prevalence in China over the past decades. Methods We performed a systematic review of literature reporting the prevalence of H. pylori infection in mainland China from 1990 to 2019 in the PubMed and China National Knowledge Infrastructure databases. We conducted a meta‐analysis of qualified studies using a random effects model to estimate the pooled prevalence with a 95% confidence interval (95%CI). Results A total of 412 eligible studies with 1 377 349 subjects were included. The pooled H. pylori prevalence was 44.2% (95%CI: 43.0–45.5%) in mainland China, with an estimated 589 million individuals infected with H. pylori. The prevalence was relatively high in the Northwest (51.8%, 95%CI: 47.5–56.1%), East (47.7%, 95%CI: 45.4–50.0%), and Southwest China (46.6%, 95%CI: 42.1–51.1%). The prevalence significantly decreased from 58.3% (95%CI: 50.7–65.5%) in the period 1983–1994 to 40.0% (95%CI: 38.2–41.8%) in the period 2015–2019. The prevalence increased with age, ranging from 28.0% (95%CI: 23.9–32.5%) in children and adolescents to 46.1% (95%CI: 44.5–47.6%) in adults. Conclusion Although the burden of H. pylori infections is still huge in China, the infection rate has been decreasing over the past decades. Targeted H. pylori eradication strategies may be considered in areas or populations with a high incidence of gastric cancer.

Objective Although several genome-wide association studies (GWAS) of non-cardia gastric cancer have been published, more novel association signals could be exploited by combining individual studies together, which will further elucidate the genetic susceptibility of non-cardia gastric cancer. Design We conducted a meta-analysis of two published Chinese GWAS studies (2031 non-cardia gastric cancer cases and 4970 cancer-free controls) and followed by genotyping of additional 3564 cases and 4637 controls in two stages. Results The overall meta-analysis revealed two new association signals. The first was a novel locus at 5q14.3 and marked by rs7712641 ( per-allele OR=0.84, 95% CI 0.80 to 0.88; p=1.21×10 −11 ). This single-nucleotide polymorphism (SNP) marker maps to the intron of the long non-coding RNA, lnc-POLR3G-4 (XLOC_004464), which we observed has lower expression in non-cardia gastric tumour compared with matched normal tissue (P wilcoxon signed-rank =7.20×10 −4). We also identified a new signal at the 1q22 locus, rs80142782 ( per-allele OR=0.62; 95% CI 0.56 to 0.69; p=1.71×10 ), which was independent of the previously reported SNP at the same locus, rs4072037 ( per-allele OR=0.74; 95% CI 0.69 to 0.79; p=6.28×10 −17 ). Analysis of the new SNP conditioned on the known SNP showed that the new SNP remained genome-wide significant (P conditional =3.47×10 −8). Interestingly, rs80142782 has a minor allele frequency of 0.05 in East Asians but is monomorphic in both European and African populations. Conclusion These findings add new evidence for inherited genetic susceptibility to non-cardia gastric cancer and provide further clues to its aetiology in the Han Chinese population.

We have associated variants at 1p35.2 and 6p22.1 with gastric cancer risk, indicating a role for SPOCD1 and BTN3A2 in gastric carcinogenesis.

A multitiered genetic association study of 25 215 single-nucleotide polymorphisms (SNPs) in three case-control sample sets (1446 patients and 1432 controls) identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with psoriasis. Although the susceptibility effects at these SNPs were modest (joint allelic odds ratios (ORs): 0.76 to 0.78; P comb : 1.3EÀ03 to 2.50EÀ04), the association patterns were consistent across the sample sets, with the minor alleles being protective. Haplotype analyses identified one common, susceptible haplotype CCG (joint allelic OR ¼ 1.27; P comb ¼ 1.88EÀ04) and a less common, protective haplotype TTT (joint allelic OR ¼ 0.74; P comb ¼ 7.05EÀ04). In combination with the other known genetic risk factors, HLA-C, IL12B and IL23R, the variants reported here generate an 11-fold psoriasis-risk differential. Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell-derived cytokine that regulates cell-mediated immunity. These results provide the foundation for additional studies required to fully dissect the associations within this cytokine-rich genomic region, as polymorphisms in closely linked candidate genes, such as IRF1, IL5 or IL4, may be driving these results through linkage disequilibrium.