The elucidation of the genetic mechanisms leading to gastrointestinal (GI) disease is my main goal. With special focus 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. I also study how the genetic make-up of the host affects the composition of the human microbiota, and ts relevance to human disease. I am interested in the potential to correlate genetics and microbiota variation with human bowel behavior and function, particularly in relation to endophenotypes of IBS (colonic transit, stool frequency etc.). Below a few recent publications by subject area, full list further down.
Irritable bowel syndrome (IBS):
A heritable component of IBS is recognized, yet no unequivocal IBS risk genes have been identified. We believe the current IBS “label” is inadequate to capture the true spectrum of a IBS manifestations, where the weight of genetic factors may range from rare single-gene forms to extremely complex polygenic conditions. We aim to unravel key IBS pathogenetic mechanisms by combining genome-wide association studies (GWAS) of common risk variants in the general population, targeted and whole-exome sequencing for the identification of rare variants in subsets of IBS patients, and functional characterization of risk genes and associated causative alleles. We have established an extensive network of collaboration with many expert clinical centers around the world, and coordinate the bellygenes initiative (www.bellygenes.org).
TRPM8 polymorphisms associated with increased risk of IBS-C and IBS-M.
Gut 2017 Sep;66(9):1725-1727
Inflammatory bowel disease (IBD)
Crohn’s disease (CD) and ulcerative colitis (UC) show a strong genetic component, and more than 200 IBD risk loci have been already discovered. We aim to exploit this information for the identification of novel diagnostic and/or therapeutic targets, and for the delineation of genotype-based strategies to personalized medicine.
C13orf31 (FAMIN) is a central regulator of immunometabolic function.
Nat. Immunol. 2016 Sep;17(9):1046-56
A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.
Nat Commun 2016 Aug;7():12342
Other GI conditions:
A genetic component has been reported also for gastroesophageal reflux disease (GERD), microscopic colitis, diverticulitis and other GI diseases but, similar to IBS, this is underinvestigated. We are running initial GWAS and targeted analyses, with the overarching goal to fill the knowledge gap and gain increased pathogenetic understanding. For these studies as well, we have established an international network of collaboration.
A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population.
Neurogastroenterol. Motil. 2017 Feb;29(2):
HLA Associations Distinguish Collagenous From Lymphocytic Colitis.
Am. J. Gastroenterol. 2016 08;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
Genes, microbiota and gut function:
Variation in the composition of gut microbiota is of relevance to human diseases but still poorly understood are the factors that induce and/or maintain such variation. We study this interaction to understand whether, and if so how, the genetic make-up of the host affects the composition of the human microbiota, and approach this question through computational assessment of host genome vs microbiome comparisons. We are 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).
Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota.
Nat. Genet. 2016 Nov;48(11):1396-1406
Stool frequency is associated with gut microbiota composition.
Gut 2017 Mar;66(3):559-560