skip to primary navigationskip to content
 

Dr Chris Wallace

Dr Chris Wallace

genetics and genomics of immune mediated diseases

Chris Wallace is accepting applications for PhD students.


Research Interests

I am a statistician who works with biological datasets to understand the mechanisms underlying human immune-mediated diseases and identify possible treatments.

During the GWAS era, we, and others, identified many genetic polymorphisms that alter risk of human immune mediated diseases such as type 1 diabetes and rheumatoid arthritis. I now follow up this research in three directions:

 

1. jointly analysing multiple immune-mediated diseases/traits to borrow information between them and understand shared and distinct components of risk 2. identifying the cell specific mechanisms through which these variants affect disease risk 3. understanding how the immune system is dysregulated in disease, and how this may be modulated

 

Statistically, my current work is focused on variable selection, Bayesian model averaging and empirical Bayes false discovery rates, and matrix factorisation, applied to integrated analysis of multiple related genetic and genomic datasets.

 

I am funded by the Wellcome Trust as a Senior Research Fellow and PI in the Department of Medicine (University of Cambridge) and hold an honorary Programme Leader position at the MRC Biostatistics Unit. I am a member of the MRC funded stratified medicine programme CLUSTER, working with partners at GOSH, QMUL, Manchester, and Liverpool on childhood arthritis.

Keywords

genomics ; genetics ; allelic expression imbalance ; variable selection ; Bayesian model averaging ; mixture models

Topics

  • type I diabetes

Key Publications

Stochastic search and joint fine-mapping increases accuracy and identifies previously unreported associations in immune-mediated diseases Asimit J, Rainbow D, Fortune M, Grinberg N, Wicker L, Wallace C. Nat. Commun. 2019

 

Fine mapping chromatin contacts in capture Hi-C data. Eijsbouts C, Burren O, Newcombe P, Wallace C. BMC genomics 2019.

 

Genetically distinct clinical subsets, and associations with asthma and eosinophil abundance, within Eosinophilic Granulomatosis with Polyangiitis Lyons P, Peters J, Alberici F, Liley J, Coulson R, Astle W, Baldini C, Bonatti F, Cid M, Elding H, Emmi G, Epplen J, Guillevin L, Jayne D, Jiang T, Gunnarsson I, Lamprecht P, Leslie S, Little M, Martorana D, Moosig F, Neumann T, Ohlsson S, Quickert S, Ramirez G, Rewerska B, Schett G, Sinico R, Szczeklik W, Tesar V, Vukcevic D, Terrier B, Watts R, Vaglio A, Holle J, Wallace C, Smith K. bioRxiv 2018.

 

simGWAS: a fast method for simulation of large scale case-control GWAS summary statistics Fortune M, Wallace C. Bioinformatics 2018.

 

Chromosome contacts in activated T cells identify autoimmune disease candidate genes Burren O, Rubio García A, Javierre B, Rainbow D, Cairns J, Cooper N, Lambourne J, Schofield E, Castro Dopico X, Ferreira R, Coulson R, Burden F, Rowlston S, Downes K, Wingett S, Frontini M, Ouwehand W, Fraser P, Spivakov M, Todd J, Wicker L, Cutler A, Wallace C. Genome Biology 2017

 

Lineage-specific genome architecture links disease variants to target genes Javierre B, Burren O, Wilder S, Kreuzhuber R, Hill S, Sewitz S, Cairns J, Wingett S, Várnai C, Thiecke M, Burden F, Farrow S, Cutler A, Rehnstrom K, Downes K, Grassi L, Kostadima M, Freire-Pritchett P, Wang F, The BLUEPRINT Consortium , Stunnenberg H, Todd J, Zerbino D, Stegle O, Ouwehand W, *Frontini M , *Wallace C, *Spivakov M , *Fraser P . Cell 2016.

 

Wallace C. Statistical testing of shared genetic control for potentially related traits. Genet Epidemiol. 2013 Dec;37(8):802-13.

 

Pekalski ML, Ferreira RC, Coulson RM, Cutler AJ, Guo H, Smyth DJ, Downes K, Dendrou CA, Castro Dopico X, Esposito L, Coleman G, Stevens HE, Nutland S, Walker NM, Guy C, Dunger DB,Wallace C, Tree TI, Todd JA, Wicker LS. Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors. J Immunol. 2013 Mar 15;190(6):2554-66.

 

Yang X, Todd JA, Clayton D, Wallace C. Extra-binomial variation approach for analysis of pooled DNA sequencing data. Bioinformatics. 2012 Nov 15;28(22):2898-904.

 

Wallace C, Rotival M, Cooper JD, Rice CM, Yang JH, McNeill M, Smyth DJ, Niblett D, Cambien F; Cardiogenics Consortium, Tiret L, Todd JA, Clayton DG, Blankenberg S. Statistical colocalization of monocyte gene expression and genetic risk variants for type 1 diabetes. Hum Mol Genet. 2012 Jun 15;21(12):2815-24.

 

Davison LJ, Wallace C, Cooper JD, Cope NF, Wilson NK, Smyth DJ, Howson JM, Saleh N, Al-Jeffery A, Angus KL, Stevens HE, Nutland S, Duley S, Coulson RM, Walker NM, Burren OS, Rice CM, Cambien F, Zeller T, Munzel T, Lackner K, Blankenberg S; Cardiogenics Consortium, Fraser P, Gottgens B, Todd JA, Attwood T, Belz S, Braund P, Cambien F, Cooper J, Crisp-Hihn A, Diemert P, Deloukas P, Foad N, Erdmann J, Goodall AH, Gracey J, Gray E, Gwilliams R, Heimerl S, Hengstenberg C, Jolley J, Krishnan U, Lloyd-Jones H, Lugauer I, Lundmark P, Maouche S, Moore JS, Muir D, Murray E, Nelson CP, Neudert J, Niblett D, O'Leary K, Ouwehand WH, Pollard H, Rankin A, Rice CM, Sager H, Samani NJ, Sambrook J, Schmitz G, Scholz M, Schroeder L, Schunkert H, Syvannen AC, Tennstedt S, Wallace C. Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene. Hum Mol Genet. 2012 Jan 15;21(2):322-33.

 

Wallace C, Smyth DJ, Maisuria-Armer M, Walker NM, Todd JA, Clayton DG. The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nat Genet. 2010 Jan;42(1):68-71.

 

Heinig M, Petretto E, Wallace C, Bottolo L, Rotival M, Lu H, Li Y, Sarwar R, Langley SR, Bauerfeind A, Hummel O, Lee YA, Paskas S, Rintisch C, Saar K, Cooper J, Buchan R, Gray EE, Cyster JG, Consortium C, Erdmann J, Hengstenberg C, Maouche S, Ouwehand WH, Rice CM, Samani NJ, Schunkert H, Goodall AH, Schulz H, Roider HG, Vingron M, Blankenberg S, Münzel T, Zeller T, Szymczak S, Ziegler A, Tiret L, Smyth DJ, Pravenec M, Aitman TJ, Cambien F, Clayton D, Todd JA, Hubner N, and Cook SA.  A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. Nature, 2010 467:460-464

 

Downes K, Pekalski M, Angus KL, Hardy M, Nutland S, Smyth DJ, Walker NM, Wallace C, and Todd JA. Reduced expression of IFIH1 is protective for type 1 diabetes. PLoS One, 2010 5.