PMID- 37347142
OWN - NLM
STAT- MEDLINE
DCOM- 20230822
LR  - 20231213
IS  - 1536-4801 (Electronic)
IS  - 0277-2116 (Print)
IS  - 0277-2116 (Linking)
VI  - 77
IP  - 3
DP  - 2023 Sep 1
TI  - Exome Sequencing Implicates DGKZ , ESRRA , and GXYLT1 for Modulating Granuloma 
      Formation in Crohn Disease.
PG  - 354-357
LID - 10.1097/MPG.0000000000003873 [doi]
AB  - 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.
CI  - Copyright (c) 2023 by European Society for European Society for Pediatric 
      Gastroenterology, Hepatology, and Nutrition and North American Society for 
      Pediatric Gastroenterology, Hepatology, and Nutrition.
FAU - Harris, R Alan
AU  - Harris RA
AD  - From the Department of Molecular and Human Genetics, Human Genome Sequencing 
      Center, Baylor College of Medicine, Houston, TX.
FAU - Bush, Allyson H
AU  - Bush AH
AD  - the Department of Pediatrics, Section of Gastroenterology, Hepatology and 
      Nutrition, Baylor College of Medicine/Texas Children's Hospital, Houston, TX.
FAU - Eagar, Todd N
AU  - Eagar TN
AD  - the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 
      Houston, TX.
AD  - the Department of Pathology and Laboratory Medicine, Weill Cornell Medical 
      College, New York, NY.
FAU - Qian, Justin
AU  - Qian J
AD  - the Department of Pediatrics, Section of Gastroenterology, Hepatology and 
      Nutrition, Baylor College of Medicine/Texas Children's Hospital, Houston, TX.
FAU - Greenwood, Michael P
AU  - Greenwood MP
AD  - the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 
      Houston, TX.
AD  - the Department of Pathology and Laboratory Medicine, Weill Cornell Medical 
      College, New York, NY.
FAU - Opekun, Antone R
AU  - Opekun AR
AD  - the Department of Pediatrics, Section of Gastroenterology, Hepatology and 
      Nutrition, Baylor College of Medicine/Texas Children's Hospital, Houston, TX.
FAU - Baldassano, Robert
AU  - Baldassano R
AD  - the Division of Gastroenterology, Hepatology and Nutrition, University of 
      Pennsylvania, Children's Hospital of Philadelphia, Philadelphia, PA.
FAU - Guthery, Stephen L
AU  - Guthery SL
AD  - the Department of Pediatrics, University of Utah and Intermountain Primary 
      Children's Hospital, Salt Lake City, UT.
FAU - Noe, Joshua D
AU  - Noe JD
AD  - the Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, 
      and Nutrition, Medical College of Wisconsin, Milwaukee, WI.
FAU - Otley, Anthony
AU  - Otley A
AD  - IWK Health/Dalhousie University, Halifax, Nova Scotia, Canada.
FAU - Rosh, Joel R
AU  - Rosh JR
AD  - Goryeb Children's Hospital/Atlantic Children's Health, Morristown, NJ.
FAU - Kugathasan, Subra
AU  - Kugathasan S
AD  - the Departments of Pediatrics and Human Genetics at Emory University School of 
      Medicine, Atlanta, GA.
FAU - Kellermayer, Richard
AU  - Kellermayer R
AD  - the Department of Pediatrics, Section of Gastroenterology, Hepatology and 
      Nutrition, Baylor College of Medicine/Texas Children's Hospital, Houston, TX.
AD  - the Children's Nutrition and Research Center, Houston, TX.
LA  - eng
GR  - P30 DK056338/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230622
PL  - United States
TA  - J Pediatr Gastroenterol Nutr
JT  - Journal of pediatric gastroenterology and nutrition
JID - 8211545
RN  - EC 2.4.2.n2 (GXYLT1 protein, human)
RN  - EC 2.7.1.107 (DGKZ protein, human)
SB  - IM
MH  - Child
MH  - Humans
MH  - *Crohn Disease/complications
MH  - Exome Sequencing
MH  - Genetic Predisposition to Disease
MH  - Granuloma/genetics/pathology
MH  - Phenotype
MH  - ERRalpha Estrogen-Related Receptor
PMC - PMC10528115
MID - NIHMS1910326
COIS- Dr Otley reports Advisory Board for AbbVie; research funding from AbbVie, 
      Janssen, Takeda, Lilly, and Pfizer. The remaining authors report no conflicts of 
      interest.
EDAT- 2023/06/22 13:09
MHDA- 2023/08/21 06:42
PMCR- 2024/09/01
CRDT- 2023/06/22 10:02
PHST- 2024/09/01 00:00 [pmc-release]
PHST- 2023/08/21 06:42 [medline]
PHST- 2023/06/22 13:09 [pubmed]
PHST- 2023/06/22 10:02 [entrez]
AID - 00005176-990000000-00416 [pii]
AID - 10.1097/MPG.0000000000003873 [doi]
PST - ppublish
SO  - J Pediatr Gastroenterol Nutr. 2023 Sep 1;77(3):354-357. doi: 
      10.1097/MPG.0000000000003873. Epub 2023 Jun 22.