The elucidation of the genetic mechanisms leading to gastrointestinal (GI) disease is my main goal. My research focus is on inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other GI conditions. I strive to identify risk genes and their causative variants by applying genetic, bioinformatic and functional genomic approaches.
Genes, microbiota and gut function
Variation in the composition of gut microbiota is of relevance to human diseases but still incompletely understood are the factors that induce and/or maintain such variation. I study how the genetic make-up of the host affects the composition of the human microbiota. I am also interested in the potential to correlate microbiota variation with human bowel behavior and function, particularly in relation to endophenotypes of IBS (colonic transit, stool frequency etc).
Selected recent publications (> 50 articles 2011-2016)
C13orf31 (FAMIN) is a central regulator of immunometabolic function.
Nat. Immunol. 2016 Sep;17(9):1046-56
Stool frequency is associated with gut microbiota composition.
Gut 2016 Apr;():
A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.
Nat Commun 2016 Aug;7():12342
A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition.
Gastroenterology 2016 Oct;151(4):724-32
A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population.
Neurogastroenterol. Motil. 2016 Aug;():
HLA Associations Distinguish Collagenous From Lymphocytic Colitis.
Am. J. Gastroenterol. 2016 Aug;111(8):1211-3
Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction.
Gastroenterology 2015 Apr;148(4):771-782.e11
HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants.
Nat. Genet. 2014 Oct;46(10):1131-4
Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.
Gastroenterology 2014 Jun;146(7):1659-68
Germline genetic contributions to risk for esophageal adenocarcinoma, Barrett's esophagus, and gastroesophageal reflux.
J. Natl. Cancer Inst. 2013 Nov;105(22):1711-8
Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies.
Gastroenterology 2013 Aug;145(2):339-47
The impact of Crohn's disease genes on healthy human gut microbiota: a pilot study.
Gut 2013 Jun;62(6):952-4
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
Nature 2012 Nov;491(7422):119-24
Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.
Nat. Genet. 2011 Oct;43(11):1066-73
Association of TNFSF15 polymorphism with irritable bowel syndrome.
Gut 2011 Dec;60(12):1671-7
CD98 expression modulates intestinal homeostasis, inflammation, and colitis-associated cancer in mice.
J. Clin. Invest. 2011 May;121(5):1733-47
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
Nat. Genet. 2011 Mar;43(3):246-52