Exome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma Formation in Crohn Disease.

TitleExome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma Formation in Crohn Disease.
Publication TypeJournal Article
Year of Publication2023
AuthorsHarris, RA, Bush, AH, Eagar, TN, Qian, J, Greenwood, MP, Opekun, AR, Baldassano, R, Guthery, SL, Noe, JD, Otley, A, Rosh, JR, Kugathasan, S, Kellermayer, R
JournalJ Pediatr Gastroenterol Nutr
Date Published2023 Sep 01
KeywordsChild, Crohn Disease, ERRalpha Estrogen-Related Receptor, Exome Sequencing, Genetic Predisposition to Disease, Granuloma, Humans, Phenotype

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used to predict deleteriousness of SNPs. Human leukocyte antigen (HLA) haplotype findings were compared to a control group (n = 8496). PLINK-based analysis between GCD and NGCD groups did not find consistently significant hits. gnomAD control comparisons, however, showed consistent subgroup associations with DGKZ , ESRRA , and GXYLT1 , genes that have been implicated in mammalian granulomatous inflammation. Our findings may guide future research and precision medicine.

Alternate JournalJ Pediatr Gastroenterol Nutr
PubMed ID37347142
PubMed Central IDPMC10528115
Grant ListP30 DK056338 / DK / NIDDK NIH HHS / United States

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