Gastrointestinal Genetics

Group leader: Koldo Garcia Etxebarria, Ph.D.

Biodonostia HRI.

Strategic objectives:

The elucidation of the genetic mechanisms leading to gastrointestinal (GI) disease is the main goal of the group. With special focus on inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other GI conditions, the group strives to identify risk genes and their causative variants by applying genetic, bioinformatic and functional genomic approaches. It also studies how the genetic make-up of the host affects the composition of the human microbiota, which is highly relevant to human disease. The group is 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.).

Main lines of research:

  • 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.
  • 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 other centers around the world, and coordinate the bellygenes initiative (
  • 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.
  • 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).

Team Members

Name Surname Centre E-mail
Mauro D’amato External collaborator

Scientific Output


Published: 10 / 17

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, Ripke S Lee J, Shah T, Abedian S, Cheon JH, Cho J, Dayani NE, Franke L, Fuyuno Y, Hart A Juyal R, Juyal G, Kim WH, Morris AP, Poustchi H, Newman WG, Midha V, Orchard T, Vahedi H, Sood A, Sung JY, Malekzadeh R, Westra HJ, Yamazaki K, Yang SK, The International Multiple Sclerosis Genetics Consortium, The International IBD Genetics Consortium, Barrett JC, Alizadeh BZ, Parkes M, Thelma BK, Daly MJ, Kubo M, Anderson CA, Weersma RK.

Nat Genet. 2015; 47: 979-86. FI: 31.616 (Q1).

High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis.

Goyette P, Boucher G, Mallon D, Ellinghaus E, Jostins L, Huang H, Ripke S, Gusareva ES, Annese V, Hauser SL, Oksenberg JR, Thomsen I, Leslie S, International Inflammatory Bowel Disease Genetics Consortium, Australia and New Zealand IBDGC, Belgium IBD Genetics Consortium, Italian Group for IBD Genetic Consortium, NIDDK Inflammatory Bowel Disease Genetics Consortium, United Kingdom IBDGC, Wellcome Trust Case Control Consortium, Quebec IBD Genetics Consortium, Daly MJ, Van Steen K, Duerr RH, Barrett JC, McGovern DP, Schumm LP, Traherne JA, Carrington MN, Kosmoliaptsis V, Karlsen TH, Franke A, Rioux JD.

Nat Genet. 2015; 47: 172-9. FI: 31.616 (Q1).

RAD21 and APOB molecular defects in chronic instestinal pseudo-obstruction.

Bonora E, Bianco F, Cordeddu L, Bamshad M, Francescatto L, Dowless D, Stanghellini V, Cogliandro RF, Lindberg G, Mungans Z, Cefle K, Ozcelik T, Palanduz S, Ozturk S, Gedikbasis A, Gori A, Pippucci T, Graziano C, Volta U, Caio G, Barbara G, D’Amato M, Seri M, Katsanis N, Rome G, De Giorgio R.

Gastroenterology. 2015; 148: 771-82. FI: 18.187 (Q1).

Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multi-national case-control cohorts.

Ek WE, Reznichenko A, Ripke S, Niesler B, Zucchelli M, Rivera NV, Schmidt PT, Pedersen NL, Magnusson P, Talley NJ, Holliday EG, Houghton L, Gazouli M, Karamanolis G, Rappold G, Burwinkel B, Surowy H, Rafter J, Assadi G, Li L, Papadaki E, Gambaccini D, Marchi S, Colucci R, Blandizzi C, Barbaro R, Karling P, Walter S, Ohlsson B, Tornblom H, Bresso F, Andreasson A, Dlugosz A, Simren M, Agreus L, Lindberg G, Boeckxstaens G, Bellini M, Stanghellini V, Barbara G, Daly MJ, Camilleri M, Wouters MM, D'Amato M.

Gut. 2015; 64: 1774-82. FI: 14.921 (Q1).

Increased serum levels of lipopolysaccharide and anti-flagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome.

Dlugosz A, Nowak P, D’Amato M, Kermani GM, Nystrom J, Abdurahman S, Lindberg G.

Neurogastroenterol Motil. 2015; 27: 1747-54. FI: 3.310 (Q2).

Severe, gastrointestinal dysmotility developed after treatment with gonadotropin-releasing hormone analogs.

Cordeddu L, Bergvall M, Sand E, Roth B, Papadaki E, Li L, D’Amato M, Ohlsson B.

Scand J Immunol. 2015; 50:291-299. FI: 2.199 (Q3).

Pathway-based Genome-wide Association Studies Reveal the Association Between Growth Factor Activity and Inflammatory Bowel Disease.

Li J, Wei Z, Chang X, Cardinale CJ, Kim CE, Baldassano RN, Hakonarson H.

Inflammatory Bowel Diseases. 2016; 22: 1540-1551. FI: 4,525 (Q1).

Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.

Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, Park YR, Raychaudhuri S, Pouget JG, Huebenthal M, Folseraas T, Wang Y, Esko T, Metspalu A, Westra HJ, Franke L, Pers TH, Weersma RK, Collij V, D'Amato M, Halfvarson J, Jensen AB, Lieb W, Degenhardt F, Forstner AJ, Hofmann A, Schreiber S, Mrowietz U, Juran BD, Lazaridis KN, Brunak S, Dale AM, Trembath RC, Weidinger S, Weichenthal M, Ellinghaus E, Elder JT, Barker, NWN, Andreassen OA, McGovern DP, Karlsen TH, Barrett JC, Parkes M, Brown MA, Franke A, IIBDGC, IGAS, IPSCSG, GAPC, PAGE.

Nature Genetics. 2016; 48: 510-510. FI: 27,959 (Q1).

Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study.

Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, Andersen V, Andrews JM, Annese V, Brand S, Brant SR, Cho JH, Daly MJ, Dubinsky M, Duerr RH, Ferguson LR, Franke A, Gearry RB, Goyette P, Hakonarson H, Halfvarson J, Hov JR, Huang H, Kennedy NA, Kupcinskas L, Lawrance IC, Lee JC, Satsangi J, Schreiber S, Théâtre E, van der Meulen-de Jong AE, Weersma RK, Wilson DC, International Inflammatory Bowel Disease Genetics Consortium, Parkes M, Vermeire S, Rioux JD, Mansfield J, Silverberg MS, Radford-Smith G, McGovern DP, Barrett JC, Lees CW.

Lancet. 2016; 387: 156-167. FI: 47,831 (Q1).

Functional Analyses of the Crohn’s Disease Risk Gene LACC1.

Assadi G, Vesterlund L, Bonfiglio F, Mazzurana L, Cordeddu L, Schepis D, Mjösberg J, Ruhrmann S, Fabbri A, Vukojevic V, Percipalle P, Salomons FA, Laurencikiene J, Törkvist L, Halfvarson J, D'Amato M. F

Plos One. 2016; 11: -. FI: 2,806 (Q1).


Published: 0 / 0


Published: 0 / 0


Published: 1 / 1

HLA Associations Distinguish Collagenous From Lymphocytic Colitis.

Westerlind H, Bonfiglio F, Mellander MR, Huebenthal M, Brynedal B, Bjork J, Torkvist L, Padyukov L, Ohlsson B, Lofberg R, Hultcrantz R, Franke A, Bresso F, D'Amato M.

American Journal Of Gastroenterology. 2016; 111: 1211-1213. FI: 9,566 (Q1).


Published: 0 / 0


Projects 2 / 2

Variantes genéticas de los canales iónicos como factores de riesgo genético en el síndrome del intestino irritable.

Investigador Principal: Mauro D’Amato. Entidad Financiadora: Gobierno Vasco, Departamento de Salud. Año inicio: 2016. Año final: 2017.

IBD-Character: Inflammatory Bowel Disease Characterization by a Multi-Modal Integrated Biomarker Study.

Investigador Principal: Jack Satsangi, Edinburgh University. Entidad Financiadora: EU-FP7. Año inicio: 2013. Año final: 2016.