Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Barrett, Jeffrey C.; Lee, James C.; Lees, Charlie W; Prescott, Natalie J.; Anderson, Carl A.; Phillips, Anne; Wesley, Emma; Parnell, Kirstie; Hu, Zhang; Drummond, Hazel E.; Nimmo, Elaine R.; Massey, Dunecan; Blaszczyk, Kasia; Elliott, Timothy R.; Cotterill, Lynn; Dallal, Helen; Lobo, Alan; Mowat, Craig; Sanderson, Jeremy; Jewell, D P; Newman, William G.; Edwards, Cathryn; Ahmad, Tariq; Mansfield, John C.; Satsangi, Jack; Parkes, Miles; Mathew, Christopher G.; Donnelly, Peter; Peltonen, Leena; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Craddock, Nicholas John; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; McCarthy, Mark I.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen; Samani, Nilesh J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas; Spencer, Chris C. A.; Bellenguez, Céline; Davison, Daniel B.; Freeman, Colin; Strange, Amy; Langford, Cordelia; Hunt, Sarah; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Perez, Marc L.; Potter, Simon; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew J.; Weston, Paul A.; Widaa, Sara; Whittaker, Pamela; Attwood, Antony; Stephens, Jonathan; Sambrook, Jennifer; Ouwehand, Willem H.; McArdle, Wendy L.; Ring, Susan M.; Strachan, David P.

doi:10.1038/ng.483

Cited by 475 publications

(265 citation statements)

References 36 publications

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“…This finding was replicated later by independent UC association studies (11,32). Additionally, the Wellcome Trust Case Control Consortium 2 (WTCCC 2) study of 15 complex disorders and traits reported a GWA scan in UC This study replicated the number of loci previously reported by Fisher et al (5) to be associated ECM1 with UC (33). Ankylosing spondylitis, like UC, is a chronic inflammatory disease, and there is a frequent clinical overlap between them.…”

Section: Discussionsupporting

confidence: 77%

Extracellular matrix protein 1 gene rs3737240 single nucleotide polymorphism is associated with ulcerative colitis in Turkish patients

Adali

Tunalı²,

Yorulmaz³

et al. 2017

Turk J Gastroenterol

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Section: Discussionsupporting

confidence: 77%

Extracellular matrix protein 1 gene rs3737240 single nucleotide polymorphism is associated with ulcerative colitis in Turkish patients

Adali

Tunalı²,

Yorulmaz³

et al. 2017

Turk J Gastroenterol

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“…The methods and quality control have been described in greater detail elsewhere 22 as part of the WTCCC2 project. 23 In total, 2329 genotyped individuals were available for whom phenotype information at age 12 were also available.…”

Section: Materials and Methods Participantsmentioning

confidence: 99%

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

et al. 2013

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The consequence of reduced cognitive ability from inbreeding has long been investigated, mainly restricted to cousin-cousin marriages. Molecular genetic techniques now allow us to test the relationship between increased ancestral inbreeding and cognitive ability in a population of traditionally unrelated individuals. In a representative UK sample of 2329 individuals, we used genome-wide SNP data to estimate the percentage of the genome covered by runs of homozygous SNPs (ROH). This was tested for association with general cognitive ability, as well as measures of verbal and non-verbal ability. Further, association was tested between these traits and specific ROH. Burden of ROH was not associated with cognitive ability after correction for multiple testing, although burden of ROH was nominally associated with increased non-verbal cognitive ability (P ¼ 0.03). Moreover, although no individual ROH was significantly associated with cognitive ability, there was a significant bias towards increased cognitive ability in carriers of ROH (P ¼ 0.002). A potential explanation for these results is increased positive assortative mating in spouses with higher cognitive ability, although we found no evidence in support of this hypothesis in a separate sample. Reduced minor allele frequency across the genome was associated with higher cognitive ability, which could contribute to an apparent increase in ROH. This may reflect minor alleles being more likely to be deleterious.

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“…Genome-wide association studies have identified genes contributing to susceptibility to Crohn's disease and ulcerative colitis. Many of these susceptibility loci play a role in immune responses to microbial signalling and processing (11) as well as epithelial barrier integrity (12,13) . Germ-free animal models of colitis indicate that the microbiota drives inflammation in genetically susceptible hosts (14) .…”

Section: Dysbiosis In Inflammatory Bowel Diseasesmentioning

confidence: 99%

The microbiome in inflammatory bowel disease and its modulation as a therapeutic manoeuvre

Hart

Hendy

2014

Proc. Nutr. Soc.

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Inflammatory bowel disease (IBD) is increasing in incidence in both the developed and the developing world. Genetic, immunological and environmental factors are known to be involved. Genome-wide studies have examined the contribution played by host genetics in the development of IBD and have estimated that genetic factors are responsible for about 25 % of the disease risk. Having an IBD-associated genotype does not always lead to development of the disease phenotype, and hence it seems likely that environmental factors are key to triggering development of the disease in genetically susceptible individuals. The gut microbiota contains more cells than its human host, and mounting evidence attests to the importance of the microbiota in the development of several diseases, including IBD, metabolic syndrome and CVD. The present paper reviews the interplay between the microbiota and the mucosal immune system in health and in IBD; and discusses the evidence base for the use of therapeutic modulation of the microbiota to prevent and treat IBD.

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Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Cited by 475 publications

References 36 publications

Extracellular matrix protein 1 gene rs3737240 single nucleotide polymorphism is associated with ulcerative colitis in Turkish patients

Extracellular matrix protein 1 gene rs3737240 single nucleotide polymorphism is associated with ulcerative colitis in Turkish patients

Genome-wide estimates of inbreeding in unrelated individuals and their association with cognitive ability

The microbiome in inflammatory bowel disease and its modulation as a therapeutic manoeuvre

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