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Genetics //

Samarani S, Mack DR, Bernstein CN, Iannello A, Debbeche O, Jantchou P, Faure C, Deslandres C, Amre DA, Ahmad A. Activating Killer-cell Immunoglobulin-like Receptor genes confer risk for Crohn’s disease in children and adults of the Western European descent: Findings based on case-control studies. PLOS One 2019;14(6):e0217767. Published 2019 Jun 13

Killer-cell Immunoglobulin-like Receptor genes encode receptors, which are mainly expressed on, and control functional activities of, Natural Killer (NK) cells. These cells are important in the inflammatory response. Activated NK cells can potentially cause tissue destruction, which might be important in development Crohn disease. In this study we performed case control studies on three independent Canadian Crohn’s disease patient cohorts (all of Western European descent): two comprising children [one from Montreal (438 children) and one from Ottawa (213 children)] and one comprising predominantly adults (from Winnipeg having 364 adults)]. We assess the gene types for for activating Killer-cell Immunoglobulin-like Receptor. We observed strong associations between all the six Killer-cell Immunoglobulin-like Receptor genes and Crohn’s disease in Ottawa children. The results were mostly replicated in the Montreal cohort of children nd the Winnipeg cohort of adults. Similarly associations between five genes were observed in the adult Winnipeg cohort. An overall analysis for all cohorts showed strong associations with four of the genes, with the strongest association evident for a gene called KIR2DS5. In the combined analysis for four Killer-cell Immunoglobulin-like Receptor genes, individuals carrying one or more of the Killer-cell Immunoglobulin-like Receptor genes were at significantly higher risks for acquiring Crohn’s disease.

We concluded that activating Killer-cell Immunoglobulin-like Receptor genes are associated with risk for developing CD in both children and adults. 

 

Frenkel S, Bernstein CN, Sargent M, Kuang Q, Jiang W, Wei J, Thiruvahindrapuram B, Spriggs E, Scherer SW, Hu P. Genome-wide analysis identifies rare copy number variations associated with inflammatory bowel disease. PLOS One 2019; 14(6): e0217846. Published 2019 Jun 11.

We hypothesized that rare (<0.1% population frequency) gene copy number variations (CNVs) could play an important mechanism for risk of IBD. We aimed to examine changes in DNA copy number in a population-based cohort of patients with IBD and search for novel genetic risk factors for IBD. DNA samples from 243 individuals with IBD from the Manitoba IBD Cohort Study and 2988 healthy controls were analyzed using genome-wide SNP microarray technology. We identified IBD-associated genes affected by rare CNV from comparing the number of overlapping CNVs in IBD samples with the number of overlapping CNVs in controls for each gene. 4,402 CNVs detected by two or three algorithms intersected 7,061 genes, in at least one analyzed sample. Four genes (e.g. DUSP22 and IP6K3) intersected by rare deletions and fourteen genes (e.g. SLC25A10, PSPN, GTF2F1) intersected by rare duplications demonstrated significant association with IBD (FDR-adjusted p-value < 0.01). Of these, ten genes were functionally related to immune response and intracellular signalling pathways. Some of these genes were also identified in other IBD related genome-wide association studies. These suggested that the identified genes may play a role in the risk of IBD.

Our results revealed new genomic loci associated with IBD, which suggested the role of rare CNVs in IBD risk.

Frenkel S, Bernstein CN, Jin YW, Sargent M, Kuang Q, Jiang W, Wei J, Thiruvahindrapuram B, Scherer SW, Hu P. Genome-wide copy number variant data for inflammatory bowel disease in a Caucasian population. Data in Brief 2019; Jul 2; 25:104203.

 

Genome-wide copy-number association studies offer new opportunities to identify the mechanisms underlying complex diseases, including chronic inflammatory, psychiatric disorders and others. We have used genotyping microarrays to analyse the copy-number variants (CNVs) from 243 Caucasian individuals with inflammatory bowel disease. The CNV data was obtained by using multiple quality control measures and merging the results of three different CNV detection algorithms: PennCNV, iPattern, and QuantiSNP. The final dataset contains 4,402 CNVs detected by two or three algorithms independently with high confidence. This paper provides a detailed description of the data generation and quality control steps. For further interpretation of the data presented in this article, please see the research article entitled Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease.