The Huang lab leads and contributes to inflammatory bowel diseases (IBD) genetics studies through collaborations with the international IBD genetics consortium (IIBDGC), the Daly Lab, the Xavier Lab and as a member of the Center for the Study of IBD at the Massachusetts General Hospital. Dr. Huang led the IIBDGC fine-mapping project which developed a novel fine-mapping method and applied it on ~ 70,000 European samples. This effort mapped 45 IBD associations to single variants with over 50% casual probabilities, significantly advancing our knowledge in IBD genetics (Huang et. al., Nature 2017). Following this study, the Huang lab focuses on understanding the tissue-specific gene regulations in the non-coding genome and their connections with IBD genetics, studies combining exome-sequencing and fine-mapping to reveal the genetic basis of IBD across the full allelic spectrum, and studies to understand the IBD genetic architecture cross major world populations.
Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative ColitisSmillie CS, Biton M, Ordovas-Montanes J, Sullivan KM, Burgin G, Graham DB, Herbst RH, Rogel N, Slyper M, Waldman J, Sud M, Andrews E, Velonias G, Haber AL, Jagadeesh K, Vickovic S, Yao J, Stevens C, Dionne D, Nguyen LT, Villani AC, Hofree M, Creasey EA, Huang H, Rozenblatt-Rosen O, Garber JJ, Khalili H, Desch AN, Daly MJ, Ananthakrishnan AN, Shalek AK, Xavier RJ, Regev A. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell. 2019 Jul 25;178(3):714-730.e22. [DOI] [PubMed] [PubMed Central]
Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitisMoran CJ, Huang H, Rivas M, Kaplan JL, Daly MJ, Winter HS. Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis. PLoS One. 2018;13(3):e0192806. eCollection 2018 [DOI] [PubMed] [PubMed Central]
Insights into the genetic epidemiology of Crohn’s and rare diseases in the Ashkenazi Jewish populationRivas MA, Avila BE, Koskela J, Huang H, Stevens C, Pirinen M, Haritunians T, Neale BM, Kurki M, Ganna A, Graham D, Glaser B, Peter I, Atzmon G, Barzilai N, Levine AP, Schiff E, Pontikos N, Weisburd B, Lek M, Karczewski KJ, Bloom J, Minikel EV, Petersen BS, Beaugerie L, Seksik P, Cosnes J, Schreiber S, Bokemeyer B, Bethge J, Heap G, Ahmad T, Plagnol V, Segal AW, Targan S, Turner D, Saavalainen P, Farkkila M, Kontula K, Palotie A, Brant SR, Duerr RH, Silverberg MS, Rioux JD, Weersma RK, Franke A, Jostins L, Anderson CA, Barrett JC, MacArthur DG, Jalas C, Sokol H, Xavier RJ, Pulver A, Cho JH, McGovern DPB, Daly MJ. Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population. PLoS Genet. 2018 May;14(5):e1007329.eCollection 2018 May [DOI] [PubMed] [PubMed Central]
Late-Onset Crohn’s Disease Is A Subgroup Distinct in Genetic and Behavioral Risk Factors With UC-Like CharacteristicsLi D, Haritunians T, Landers C, Potdar AA, Yang S, Huang H, Schumm LP, Daly M, Targan SR, McGovern DPB. Late-Onset Crohn's Disease Is A Subgroup Distinct in Genetic and Behavioral Risk Factors With UC-Like Characteristics. Inflamm Bowel Dis. 2018 Oct 12;24(11):2413-2422. [DOI] [PubMed] [PubMed Central]
Fine-mapping inflammatory bowel disease loci to single-variant resolutionHailiang Huang, Ming Fang, Luke Jostins, Maša Umićević Mirkov, Gabrielle Boucher, Carl A Anderson, Vibeke Andersen, Isabelle Cleynen, Adrian Cortes, François Crins, Mauro D'Amato, Valérie Deffontaine, Julia Dmitrieva, Elisa Docampo, Mahmoud Elansary, Kyle Kai-How Farh, Andre Franke, Ann-Stephan Gori, Philippe Goyette, Jonas Halfvarson, Talin Haritunians, Jo Knight, Ian C Lawrance, Charlie W Lees, Edouard Louis, Rob Mariman, Theo Meuwissen, Myriam Mni, Yukihide Momozawa, Miles Parkes, Sarah L Spain, Emilie Théâtre, Gosia Trynka, Jack Satsangi, Suzanne van Sommeren, Severine Vermeire, Ramnik J Xavier, Rinse K Weersma, Richard H Duerr, Christopher G Mathew, John D Rioux, Dermot PB McGovern, Judy H Cho, Michel Georges, Mark J Daly, and Jeffrey C Barrett. 2017. “Fine-mapping inflammatory bowel disease loci to single-variant resolution.” Nature, 547, 7662, Pp. 173-178. Abstract
Characterization of candidate genes in inflammatory bowel disease-associated risk lociJoanna M Peloquin, Gautam Goel, Lingjia Kong, Hailiang Huang, Talin Haritunians, Balfour R Sartor, Mark J Daly, Rodney D Newberry, Dermot P McGovern, Vijay Yajnik, Sergio A Lira, and Ramnik J Xavier. 2016. “Characterization of candidate genes in inflammatory bowel disease-associated risk loci.” JCI Insight, 1, 13, Pp. e87899. Abstract
Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis RiskKara G Lassen, Craig I McKenzie, Muriel Mari, Tatsuro Murano, Jakob Begun, Leigh A Baxt, Gautam Goel, Eduardo J Villablanca, Szu-Yu Kuo, Hailiang Huang, Laurence Macia, Atul K Bhan, Marcel Batten, Mark J Daly, Fulvio Reggiori, Charles R Mackay, and Ramnik J Xavier. 2016. “Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk.” Immunity, 44, 6, Pp. 1392-405. Abstract
Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association studyIsabelle Cleynen, Gabrielle Boucher, Luke Jostins, Philip L Schumm, Sebastian Zeissig, Tariq Ahmad, Vibeke Andersen, Jane M Andrews, Vito Annese, Stephan Brand, Steven R Brant, Judy H Cho, Mark J Daly, Marla Dubinsky, Richard H Duerr, Lynnette R Ferguson, Andre Franke, Richard B Gearry, Philippe Goyette, Hakon Hakonarson, Jonas Halfvarson, Johannes R Hov, Hailang Huang, Nicholas A Kennedy, Limas Kupcinskas, Ian C Lawrance, James C Lee, Jack Satsangi, Stephan Schreiber, Emilie Théâtre, Andrea E van der Meulen-de Jong, Rinse K Weersma, David C Wilson, Miles Parkes, Severine Vermeire, John D Rioux, John Mansfield, Mark S Silverberg, Graham Radford-Smith, Dermot PB McGovern, Jeffrey C Barrett, and Charlie W Lees. 2016. “Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.” Lancet, 387, 10014, Pp. 156-67. Abstract
Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populationsJimmy Z Liu, Suzanne van Sommeren, Hailiang Huang, Siew C Ng, Rudi Alberts, Atsushi Takahashi, Stephan Ripke, James C Lee, Luke Jostins, Tejas Shah, Shifteh Abedian, Jae Hee Cheon, Judy Cho, Naser E Dayani, Lude Franke, Yuta Fuyuno, Ailsa Hart, Ramesh C Juyal, Garima Juyal, Won Ho Kim, Andrew P Morris, Hossein Poustchi, William G Newman, Vandana Midha, Timothy R Orchard, Homayon Vahedi, Ajit Sood, Joseph Y Sung, Reza Malekzadeh, Harm-Jan Westra, Keiko Yamazaki, Suk-Kyun Yang, Jeffrey C Barrett, Behrooz Z Alizadeh, Miles Parkes, Thelma Bk, Mark J Daly, Michiaki Kubo, Carl A Anderson, and Rinse K Weersma. 2015. “Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.” Nat Genet, 47, 9, Pp. 979-986. Abstract
High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitisPhilippe Goyette, Gabrielle Boucher, Dermot Mallon, Eva Ellinghaus, Luke Jostins, Hailiang Huang, Stephan Ripke, Elena S Gusareva, Vito Annese, Stephen L Hauser, Jorge R Oksenberg, Ingo Thomsen, Stephen Leslie, Mark J Daly, Kristel Van Steen, Richard H Duerr, Jeffrey C Barrett, Dermot PB McGovern, Philip L Schumm, James A Traherne, Mary N Carrington, Vasilis Kosmoliaptsis, Tom H Karlsen, Andre Franke, and John D Rioux. 2015. “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.” Nat Genet, 47, 2, Pp. 172-9. Abstract
Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal InflammationZhifang Cao, Kara L Conway, Robert J Heath, Jason S Rush, Elizaveta S Leshchiner, Zaida G Ramirez-Ortiz, Natalia B Nedelsky, Hailiang Huang, Aylwin Ng, Agnès Gardet, Shih-Chin Cheng, Alykhan F Shamji, John D Rioux, Cisca Wijmenga, Mihai G Netea, Terry K Means, Mark J Daly, and Ramnik J Xavier. 2015. “Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation.” Immunity, 43, 4, Pp. 715-26. Abstract
Differential effect of genetic burden on disease phenotypes in Crohn’s disease and ulcerative colitis: analysis of a North American cohortAshwin N Ananthakrishnan, Hailiang Huang, Deanna D Nguyen, Jenny Sauk, Vijay Yajnik, and Ramnik J Xavier. 2014. “Differential effect of genetic burden on disease phenotypes in Crohn's disease and ulcerative colitis: analysis of a North American cohort.” Am J Gastroenterol, 109, 3, Pp. 395-400. Abstract
RESULTS: Our study cohort included 1,105 patients (697 CD, 408 UC). Increasing genetic burden was associated with earlier age of diagnosis of CD (Ptrend=0.008). Patients in the highest GRS quartile were likely to develop disease 5 years earlier than those in the lowest quartile. Increasing genetic burden was also associated with ileal involvement in CD (Ptrend <0.0001). The effect of genetic burden was independent of the NOD2 locus and was stronger among those with no NOD2 variants, and in never smokers. UC patients with an involved first-degree relative had a higher genetic burden, but GRS was not associated with disease phenotype in UC.
CONCLUSIONS: Increasing genetic burden is associated with early age of diagnosis in CD, but not UC. The expanded panel of IBD risk loci explains only a fraction of variance of disease phenotype, suggesting limited clinical utility of genetics in predicting natural history.