Humoral reaction in the inflamed colon in Hirschsprung's disease and ulcerative colitis.

Armstrong, G. R.; Raafat, F.

doi:10.1136/jcp.41.9.975

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…Since this low-frequency variant was not present in the Finnish cohort and not replicated in the US cohort (P = 0.58), we hypothesize that rs144432435 is tagging a rare haplotype present in Denmark and Sweden but not in the USA. Further studies are needed to determine the presence of the novel HSCR association signal in populations of different origin and experimental studies are also needed to uncover the functional mechanism underlying the association [38]. Similarly, a previous study [12] has also detected an Asianspecific secondary HSCR association signal of low frequency at the RET locus.…”

Section: Conditional Analysis Identifies a New Low-frequency Hscr Susmentioning

confidence: 92%

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Genome-wide association study of Hirschsprung disease detects a novel low-frequency variant at the RET locus

et al. 2018

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Hirschsprung disease (HSCR) is a congenital disorder with a population incidence of ~1/5000 live births, defined by an absence of enteric ganglia along variable lengths of the colon. HSCR genome-wide association studies (GWAS) have found common associated variants at RET, SEMA3, and NRG1, but they still fail to explain all of its heritability. To enhance gene discovery, we performed a GWAS of 170 cases identified from the Danish nationwide pathology registry with 4717 controls, based on 6.2 million variants imputed from the haplotype reference consortium panel. We found a novel low-frequency variant (rs144432435), which, when conditioning on the lead RET single-nucleotide polymorphism (SNP), was of genome-wide significance in the discovery analysis. This conditional association signal was replicated in a Swedish HSCR cohort with discovery plus replication meta-analysis conditional odds ratio of 6.6 (P = 7.7 × 10; 322 cases and 4893 controls). The conditional signal was, however, not replicated in two HSCR cohorts from USA and Finland, leading to the hypothesis that rs144432435 tags a rare haplotype present in Denmark and Sweden. Using the genome-wide complex trait analysis method, we estimated the SNP heritability of HSCR to be 88%, close to estimates based on classical family studies. Moreover, by using Lasso (least absolute shrinkage and selection operator) regression we were able to construct a genetic HSCR predictor with a area under the receiver operator characteristics curve of 76% in an independent validation set. In conclusion, we combined the largest collection of sporadic Hirschsprung cases to date (586 cases) to further elucidate HSCR's genetic architecture.

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Section: Conditional Analysis Identifies a New Low-frequency Hscr Susmentioning

confidence: 92%

“…We detected a positive genetic correlation of 0.23, although not statistically significant (P = 0.09). Future studies are needed to investigate possible shared genetic architecture of these diseases [38,40].…”

Section: Genetic Correlationmentioning

confidence: 99%

Genome-wide association study of Hirschsprung disease detects a novel low-frequency variant at the RET locus

et al. 2018

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“…Controls consisted of lymphoid tissues (lymph nodes and tonsils) for IgG and IgM, small intestinal mucosa for IgA, and bronchial mucosa from autopsy of a patient with bronchial asthma for IgE. The quantitative counts of immunoglobulin-containing cells were carried out as previously described (12). Quantitative assessment of eosinophils was done using a grading system proposed by Whitington and Whitington (13).…”

Section: Methodsmentioning

confidence: 99%

Eosinophilic Proctitis with Giant Cells

Raafat,

Castro,

Booth

1990

J. pediatr. gastroenterol. nutr.

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SummaryTwo infants, subsequently shown to have cow's milk protein intolerance, presented with rectal bleeding in the first week of life. Rectal biopsies showed eosinophilic infiltration of the mucosa with several multinucleated giant cells. IgG, IgM, and IgA containing plasma cells were present but IgE could not be detected in rectal biopsies. While cow's milk protein intolerance is a well‐recognized cause of proctocolitis in infancy, eosinophilic granulomatous‐like lesions with giant cells may be a prominent feature and do not exclude the diagnosis.

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A study of mucosal gut immunity in infants who develop Hirschsprung's-associated enterocolitis

Turnock

Spitz

Ströbel

1992

Journal of Pediatric Surgery

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Humoral reaction in the inflamed colon in Hirschsprung's disease and ulcerative colitis.

Cited by 6 publications

References 9 publications

Genome-wide association study of Hirschsprung disease detects a novel low-frequency variant at the RET locus

Genome-wide association study of Hirschsprung disease detects a novel low-frequency variant at the RET locus

Eosinophilic Proctitis with Giant Cells

A study of mucosal gut immunity in infants who develop Hirschsprung's-associated enterocolitis

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