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Cambridge Immunology Network

 

Research

The overarching goal of our group is to understand the role of genetic variants in modulating the immune system with the ultimate aim to identify mechanisms through which genetic variants predispose to autoimmune diseases.

 

We are an interdisciplinary group that combines large scale genomic assays with computational methods to answer our research questions. We use statistical methods to identify genomic regions associated with the risk of autoimmune diseases. To link these associated variants to function we focus on selected immune cell types and generate genomic profiles using

(i) ChIP-sequencing to catalog active regulatory genomic sites, and

(ii) RNA-sequencing to characterise changes in gene expression. We are also interested in genotype effects on immune cell variability across individuals for which we use single cell transcriptome profiling.

Publications

Key publications: 

Gusev A, Lee SH, Trynka G, Finucane H, Vilhjálmsson BJ, Xu H, Zang C, Ripke S, Bulik-Sullivan B, Stahl E; Schizophrenia Working Group of the Psychiatric Genomics Consortium; SWE-SCZ Consortium, Kähler AK, Hultman CM, Purcell SM, McCarroll SA, Daly M, Pasaniuc B, Sullivan PF, Neale BM, Wray NR, Raychaudhuri S, Price AL; Schizophrenia Working Group of the Psychiatric Genomics Consortium; SWE-SCZ Consortium. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am J Hum Genet. 2014 Nov 6;95(5):535-52. doi: 10.1016/j.ajhg.2014.10.004. Epub 2014 Nov 6. PMID: 25439723 [PubMed - in process] 

Senapati S, Gutierrez-Achury J, Sood A, Midha V, Szperl A, Romanos J, Zhernakova A, Franke L, Alonso S, Thelma BK, Wijmenga C, Trynka G. Evaluation of European coeliac disease risk variants in a north Indian population. Eur J Hum Genet. 2014 Jul 23. doi: 10.1038/ejhg.2014.137. PMID: 25052311 [PubMed - as supplied by publisher]

Hu X, Kim H, Raj T, Brennan PJ, Trynka G, Teslovich N, Slowikowski K, Chen WM, Onengut S, Baecher-Allan C, De Jager PL, Rich SS, Stranger BE, Brenner MB and Raychaudhuri S Regulation of gene expression in autoimmune disease loci and the genetic basis of proliferation in CD4+ effector memory T cells. PLoS genetics 2014;10;6;e1004404 PUBMED: 24968232; PMC: 4072514; DOI: 10.1371/journal.pgen.1004404

Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Yoshida S, Graham RR, Manoharan A, Ortmann W, Bhangale T, Denny JC, Carroll RJ, Eyler AE, Greenberg JD, Kremer JM, Pappas DA, Jiang L, Yin J, Ye L, Su DF, Yang J, Xie G, Keystone E, Westra HJ, Esko T, Metspalu A, Zhou X, Gupta N, Mirel D, Stahl EA, Diogo D, Cui J, Liao K, Guo MH, Myouzen K, Kawaguchi T, Coenen MJ, van Riel PL, van de Laar MA, Guchelaar HJ, Huizinga TW, Dieudé P, Mariette X, Bridges SL, Zhernakova A, Toes RE, Tak PP, Miceli-Richard C, Bang SY, Lee HS, Martin J, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Rantapää-Dahlqvist S, Arlestig L, Choi HK, Kamatani Y, Galan P, Lathrop M, RACI consortium, GARNET consortium, Eyre S, Bowes J, Barton A, de Vries N, Moreland LW, Criswell LA, Karlson EW, Taniguchi A, Yamada R, Kubo M, Liu JS, Bae SC, Worthington J, Padyukov L, Klareskog L, Gregersen PK, Raychaudhuri S, Stranger BE, De Jager PL, Franke L, Visscher PM, Brown MA, Yamanaka H, Mimori T, Takahashi A, Xu H, Behrens TW, Siminovitch KA, Momohara S, Matsuda F, Yamamoto K and Plenge RM Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014;506;7488;376-81 PUBMED: 24390342; PMC: 3944098; DOI: 10.1038/nature12873

Trynka G and Raychaudhuri S  Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.Current opinion in genetics & development 2013;23;6;635-41 PUBMED: 24287333; PMC: 4073234; DOI: 10.1016/j.gde.2013.10.009

Trynka G, Sandor C, Han B, Xu H, Stranger BE, Liu XS and Raychaudhuri S  Chromatin marks identify critical cell types for fine mapping complex trait variants. Nature genetics 2013;45;2;124-30 PUBMED: 23263488; PMC: 3826950; DOI: 10.1038/ng.2504

Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K, Amos CI, Padyukov L, Toes RE, Huizinga TW, Wijmenga C, Trynka G, Franke L, Westra HJ, Alfredsson L, Hu X, Sandor C, de Bakker PI, Davila S, Khor CC, Heng KK, Andrews R, Edkins S, Hunt SE, Langford C, Symmons D, Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, Wellcome Trust Case Control Consortium, Concannon P, Onengut-Gumuscu S, Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Ärlsetig L, Martin J, Rantapää-Dahlqvist S, Plenge RM, Raychaudhuri S, Klareskog L, Gregersen PK and Worthington J High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nature genetics 2012;44;12;1336-40 PUBMED: 23143596; PMC: 3605761; DOI: 10.1038/ng.2462

Stahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, Voight BF, Kraft P, Chen R, Kallberg HJ, Kurreeman FA, Diabetes Genetics Replication and Meta-analysis Consortium, Myocardial Infarction Genetics Consortium, Kathiresan S, Wijmenga C, Gregersen PK, Alfredsson L, Siminovitch KA, Worthington J, de Bakker PI, Raychaudhuri S and Plenge RM Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nature genetics 2012;44;5;483-9 PUBMED: 22446960; PMC: 3454878; DOI: 10.1038/ng.2232

Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, Szperl A, Bakker SF, Bardella MT, Bhaw-Rosun L, Castillejo G, de la Concha EG, de Almeida RC, Dias KR, van Diemen CC, Dubois PC, Duerr RH, Edkins S, Franke L, Fransen K, Gutierrez J, Heap GA, Hrdlickova B, Hunt S, Plaza Izurieta L, Izzo V, Joosten LA, Langford C, Mazzilli MC, Mein CA, Midah V, Mitrovic M, Mora B, Morelli M, Nutland S, Núñez C, Onengut-Gumuscu S, Pearce K, Platteel M, Polanco I, Potter S, Ribes-Koninckx C, Ricaño-Ponce I, Rich SS, Rybak A, Santiago JL, Senapati S, Sood A, Szajewska H, Troncone R, Varadé J, Wallace C, Wolters VM, Zhernakova A, Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), PreventCD Study Group, Wellcome Trust Case Control Consortium (WTCCC), Thelma BK, Cukrowska B, Urcelay E, Bilbao JR, Mearin ML, Barisani D, Barrett JC, Plagnol V, Deloukas P, Wijmenga C and van Heel DA  Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nature genetics 2011;43;12;1193-201 PUBMED: 22057235; PMC: 3242065; DOI: 10.1038/ng.998

Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, Westra HJ, Fehrmann RS, Kurreeman FA, Thomson B, Gupta N, Romanos J, McManus R, Ryan AW, Turner G, Brouwer E, Posthumus MD, Remmers EF, Tucci F, Toes R, Grandone E, Mazzilli MC, Rybak A, Cukrowska B, Coenen MJ, Radstake TR, van Riel PL, Li Y, de Bakker PI, Gregersen PK, Worthington J, Siminovitch KA, Klareskog L, Huizinga TW, Wijmenga C and Plenge RM Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS genetics 2011;7;2;e1002004 PUBMED: 21383967; PMC: 3044685; DOI: 10.1371/journal.pgen.1002004

Trynka G, Wijmenga C and van Heel DA A genetic perspective on coeliac disease.Trends in molecular medicine 2010;16;11;537-50 PUBMED: 20947431; DOI: 10.1016/j.molmed.2010.09.003

Zhernakova A, Elbers CC, Ferwerda B, Romanos J, Trynka G, Dubois PC, de Kovel CG, Franke L, Oosting M, Barisani D, Bardella MT, Finnish Celiac Disease Study Group, Joosten LA, Saavalainen P, van Heel DA, Catassi C, Netea MG and Wijmenga C Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection. American journal of human genetics 2010;86;6;970-7 PUBMED: 20560212; PMC: 3032060; DOI: 10.1016/j.ajhg.2010.05.004

Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti A, Zhernakova A, Heap GA, Adány R, Aromaa A, Bardella MT, van den Berg LH, Bockett NA, de la Concha EG, Dema B, Fehrmann RS, Fernández-Arquero M, Fiatal S, Grandone E, Green PM, Groen HJ, Gwilliam R, Houwen RH, Hunt SE, Kaukinen K, Kelleher D, Korponay-Szabo I, Kurppa K, MacMathuna P, Mäki M, Mazzilli MC, McCann OT, Mearin ML, Mein CA, Mirza MM, Mistry V, Mora B, Morley KI, Mulder CJ, Murray JA, Núñez C, Oosterom E, Ophoff RA, Polanco I, Peltonen L, Platteel M, Rybak A, Salomaa V, Schweizer JJ, Sperandeo MP, Tack GJ, Turner G, Veldink JH, Verbeek WH, Weersma RK, Wolters VM, Urcelay E, Cukrowska B, Greco L, Neuhausen SL, McManus R, Barisani D, Deloukas P, Barrett JC, Saavalainen P, Wijmenga C and van Heel DA Multiple common variants for celiac disease influencing immune gene expression. Nature genetics 2010;42;4;295-302 PUBMED: 20190752; PMC: 2847618; DOI: 10.1038/ng.543

Coenen MJ, Trynka G, Heskamp S, Franke B, van Diemen CC, Smolonska J, van Leeuwen M, Brouwer E, Boezen MH, Postma DS, Platteel M, Zanen P, Lammers JW, Groen HJ, Mali WP, Mulder CJ, Tack GJ, Verbeek WH, Wolters VM, Houwen RH, Mearin ML, van Heel DA, Radstake TR, van Riel PL, Wijmenga C, Barrera P and Zhernakova A Common and different genetic background for rheumatoid arthritis and coeliac disease. Human molecular genetics 2009;18;21;4195-203 PUBMED: 19648290; DOI: 10.1093/hmg/ddp365

Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, Bruinenberg M, Heap GA, Platteel M, Ryan AW, de Kovel C, Holmes GK, Howdle PD, Walters JR, Sanders DS, Mulder CJ, Mearin ML, Verbeek WH, Trimble V, Stevens FM, Kelleher D, Barisani D, Bardella MT, McManus R, van Heel DA and Wijmenga C Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut 2009;58;8;1078-83 PUBMED: 19240061; DOI: 10.1136/gut.2008.169052

Dr Gosia  Trynka
Takes PhD students
Not available for consultancy

Affiliations

Classifications: 
Departments and institutes: 
Person keywords: 
GWAS
epigenetics
CD4+ T regulatory cells
autoimmune disease susceptibility loci
immunogenomics
single cell profiling
gene regulation