Dr Jeffrey Barrett | Director of Open Targets & Group Leader

Barrett, Jeffrey

Jeff is Director of Open Targets, an open innovation partnership to use cutting-edge genomic results to improve the early stages of drug development. His research team at Sanger analyzes thousands of genomes to better understand the biology of a wide range of complex disorders.

I believe that our rapidly advancing understanding of the genetics of complex diseases has the power to transform how we make new medicines, and prescribe them to the right patients. By collaborating with clinicians around the UK, my team combines the analysis of whole genome sequencing with functional genomics data from the right cells in the right context to connect genetics to biology.

I became interested in human disease genetics during a research project in Mark Daly's lab at the Whitehead Institute while I was a student at MIT. After graduating I joined Mark's group full-time where I developed software tools, including the widely used Haploview program. As I became interested in pursuing genetics as a career, I moved to Lon Cardon's group in Oxford for a D. Phil in Statistics. I helped design the first generation of genome-wide association studies (GWAS), and was a lead analyst for the Wellcome Trust Case Control Consortium. Contrary to my assumption that I'd move back to the States, I couldn't turn down a post-doc opportunity in David Clayton's group in Cambridge, where I worked on meta-analyses and follow-up of GWAS in both inflammatory bowel disease and type 1 diabetes, each of which resulted in the identification of twenty novel associations.

I moved to the Sanger Institute in November 2008 to start a team in medical genomics (and committing myself to the UK for the long haul!). My team has used GWAS as a tool to explore the overlapping genetic architecture of diseases of inflammation, immunity, and infection including celiac disease, inflammatory bowel disease, multiple sclerosis, tuberculosis and malaria. More recently, the team has also analyzed large scale exome-sequencing datasets to probe the contribution of rare genetic variation in developmental disorders, autism and schizophrenia.

My leadership roles have included editorships at Bioinformatics and Human Molecular Genetics, the management committees of the WTCCC3, UK10K and DDD studies, and co-chairmanship of the International IBD Genetics Consortium.

Publications

  • Fine-mapping inflammatory bowel disease loci to single-variant resolution.

    Huang H, Fang M, Jostins L, Umićević Mirkov M, Boucher G et al.

    Nature 2017;547;7662;173-178

  • The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability.

    Singh T, Walters JTR, Johnstone M, Curtis D, Suvisaari J et al.

    Nature genetics 2017

  • Prevalence and architecture of de novo mutations in developmental disorders.

    Deciphering Developmental Disorders Study

    Nature 2017;542;7642;433-438

  • Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.

    Luo Y, de Lange KM, Jostins L, Moutsianas L, Randall J et al.

    Nature genetics 2017;49;2;186-192

  • Open Targets: a platform for therapeutic target identification and validation.

    Koscielny G, An P, Carvalho-Silva D, Cham JA, Fumis L et al.

    Nucleic acids research 2017;45;D1;D985-D994

  • A reference panel of 64,976 haplotypes for genotype imputation.

    McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR et al.

    Nature genetics 2016;48;10;1279-83

  • Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

    Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH et al.

    Nature genetics 2016;48;9;1060-5

  • Genetic Complexity of Crohn's Disease in 2 Large Ashkenazi Jewish Families.

    Levine AP, Pontikos N, Schiff ER, Jostins L, Speed D et al.

    Gastroenterology 2016

  • Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders.

    Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L et al.

    Nature neuroscience 2016;19;4;571-7

  • 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 et al.

    Nature genetics 2016

  • HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.

    Sveinbjornsson G, Gudbjartsson DF, Halldorsson BV, Kristinsson KG, Gottfredsson M et al.

    Nature genetics 2016;48;3;318-22

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

    Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S et al.

    Lancet (London, England) 2016;387;10014;156-67

  • Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

    Akawi N, McRae J, Ansari M, Balasubramanian M, Blyth M et al.

    Nature genetics 2015;47;11;1363-9

  • Understanding inflammatory bowel disease via immunogenetics.

    de Lange KM and Barrett JC

    Journal of autoimmunity 2015;64;91-100

  • Strategies for fine-mapping complex traits.

    Spain SL and Barrett JC

    Human molecular genetics 2015;24;R1;R111-9

  • The UK10K project identifies rare variants in health and disease.

    UK10K Consortium, Walter K, Min JL, Huang J, Crooks L et al.

    Nature 2015;526;7571;82-90

  • Using human genetics to make new medicines.

    Barrett JC, Dunham I and Birney E

    Nature reviews. Genetics 2015;16;10;561-2

  • Class II HLA interactions modulate genetic risk for multiple sclerosis.

    Moutsianas L, Jostins L, Beecham AH, Dilthey AT, Xifara DK et al.

    Nature genetics 2015;47;10;1107-13

  • 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 et al.

    Nature genetics 2015;47;9;979-986

  • High-throughput and quantitative genome-wide messenger RNA sequencing for molecular phenotyping.

    Collins JE, Wali N, Sealy IM, Morris JA, White RJ et al.

    BMC genomics 2015;16;578

  • Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration.

    Curtis J, Luo Y, Zenner HL, Cuchet-Lourenço D, Wu C et al.

    Nature genetics 2015;47;5;523-527

  • Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data.

    Wright CF, Fitzgerald TW, Jones WD, Clayton S, McRae JF et al.

    Lancet (London, England) 2015;385;9975;1305-14

  • Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.

    Onengut-Gumuscu S, Chen WM, Burren O, Cooper NJ, Quinlan AR et al.

    Nature genetics 2015;47;4;381-6

  • Characterization of expression quantitative trait loci in the human colon.

    Singh T, Levine AP, Smith PJ, Smith AM, Segal AW and Barrett JC

    Inflammatory bowel diseases 2015;21;2;251-6

  • Pooled sequencing of 531 genes in inflammatory bowel disease identifies an associated rare variant in BTNL2 and implicates other immune related genes.

    Prescott NJ, Lehne B, Stone K, Lee JC, Taylor K et al.

    PLoS genetics 2015;11;2;e1004955

  • 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 et al.

    Nature genetics 2015;47;2;172-9

  • Genetic association of fetal-hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer.

    Mtatiro SN, Mgaya J, Singh T, Mariki H, Rooks H et al.

    BMC medical genetics 2015;16;4

  • Synaptic, transcriptional and chromatin genes disrupted in autism.

    De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K et al.

    Nature 2014;515;7526;209-15

  • A genome-wide association study of anorexia nervosa.

    Boraska V, Franklin CS, Floyd JA, Thornton LM, Huckins LM et al.

    Molecular psychiatry 2014;19;10;1085-94

  • Response to 'Predicting the diagnosis of autism spectrum disorder using gene pathway analysis'.

    Robinson EB, Howrigan D, Yang J, Ripke S, Anttila V et al.

    Molecular psychiatry 2014;19;8;859-61

  • Distribution and medical impact of loss-of-function variants in the Finnish founder population.

    Lim ET, Würtz P, Havulinna AS, Palta P, Tukiainen T et al.

    PLoS genetics 2014;10;7;e1004494

  • Guidelines for investigating causality of sequence variants in human disease.

    MacArthur DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J et al.

    Nature 2014;508;7497;469-76

  • Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania.

    Mtatiro SN, Singh T, Rooks H, Mgaya J, Mariki H et al.

    PloS one 2014;9;11;e111464

  • Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage.

    Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V et al.

    Science (New York, N.Y.) 2013;342;6160;866-71

  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.

    International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, Patsopoulos NA, Xifara DK, Davis MF et al.

    Nature genetics 2013;45;11;1353-60

  • Negligible impact of rare autoimmune-locus coding-region variants on missing heritability.

    Hunt KA, Mistry V, Bockett NA, Ahmad T, Ban M et al.

    Nature 2013;498;7453;232-5

  • Imputation-based meta-analysis of severe malaria in three African populations.

    Band G, Le QS, Jostins L, Pirinen M, Kivinen K et al.

    PLoS genetics 2013;9;5;e1003509

  • The intermediate filament protein, vimentin, is a regulator of NOD2 activity.

    Stevens C, Henderson P, Nimmo ER, Soares DC, Dogan B et al.

    Gut 2013;62;5;695-707

  • Using genetic prediction from known complex disease Loci to guide the design of next-generation sequencing experiments.

    Jostins L, Levine AP and Barrett JC

    PloS one 2013;8;10;e76328

  • Olorin: combining gene flow with exome sequencing in large family studies of complex disease.

    Morris JA and Barrett JC

    Bioinformatics (Oxford, England) 2012;28;24;3320-1

  • Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

    Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP et al.

    Nature 2012;491;7422;119-24

  • Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

    Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L et al.

    Nature genetics 2012;44;10;1137-41

  • Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

    Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL et al.

    Nature genetics 2010;42;12;1118-25

  • A map of human genome variation from population-scale sequencing.

    1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD et al.

    Nature 2010;467;7319;1061-73

  • Synthetic associations in the context of genome-wide association scan signals.

    Orozco G, Barrett JC and Zeggini E

    Human molecular genetics 2010;19;R2;R137-44

  • Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1.

    Anttila V, Stefansson H, Kallela M, Todt U, Terwindt GM et al.

    Nature genetics 2010;42;10;869-73

  • Evoker: a visualization tool for genotype intensity data.

    Morris JA, Randall JC, Maller JB and Barrett JC

    Bioinformatics (Oxford, England) 2010;26;14;1786-7

  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.

    Wellcome Trust Case Control Consortium, Craddock N, Hurles ME, Cardin N, Pearson RD et al.

    Nature 2010;464;7289;713-20

  • Multiple common variants for celiac disease influencing immune gene expression.

    Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J et al.

    Nature genetics 2010;42;4;295-302

  • Tryptophan depletion and formation of alpha-aminoadipic and gamma-glutamic semialdehydes in porcine burger patties with added phenolic-rich fruit extracts.

    Ganhão R, Morcuende D and Estévez M

    Journal of agricultural and food chemistry 2010;58;6;3541-8

  • Common variants at five new loci associated with early-onset inflammatory bowel disease.

    Imielinski M, Baldassano RN, Griffiths A, Russell RK, Annese V et al.

    Nature genetics 2009;41;12;1335-40

  • Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.

    UK IBD Genetics Consortium, Barrett JC, Lee JC, Lees CW, Prescott NJ et al.

    Nature genetics 2009;41;12;1330-4

  • Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.

    Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD et al.

    Nature genetics 2009;41;6;703-7

  • Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.

    Anderson CA, Massey DC, Barrett JC, Prescott NJ, Tremelling M et al.

    Gastroenterology 2009;136;2;523-9.e3

  • Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.

    Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH et al.

    Nature genetics 2008;40;8;955-62

  • Evaluating the effects of imputation on the power, coverage, and cost efficiency of genome-wide SNP platforms.

    Anderson CA, Pettersson FH, Barrett JC, Zhuang JJ, Ragoussis J et al.

    American journal of human genetics 2008;83;1;112-9

  • Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease.

    Fisher SA, Tremelling M, Anderson CA, Gwilliam R, Bumpstead S et al.

    Nature genetics 2008;40;6;710-2

  • Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

    Wellcome Trust Case Control Consortium, Australo-Anglo-American Spondylitis Consortium (TASC), Burton PR, Clayton DG, Cardon LR et al.

    Nature genetics 2007;39;11;1329-37

  • A second generation human haplotype map of over 3.1 million SNPs.

    International HapMap Consortium, Frazer KA, Ballinger DG, Cox DR, Hinds DA et al.

    Nature 2007;449;7164;851-61

  • Genome-wide detection and characterization of positive selection in human populations.

    Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E et al.

    Nature 2007;449;7164;913-8

  • Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility.

    Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA et al.

    Nature genetics 2007;39;7;830-2

  • Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

    Wellcome Trust Case Control Consortium

    Nature 2007;447;7145;661-78

  • Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

    Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS et al.

    Science (New York, N.Y.) 2007;316;5829;1336-41

  • A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity.

    Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM et al.

    Science (New York, N.Y.) 2007;316;5826;889-94

  • Evaluating coverage of genome-wide association studies.

    Barrett JC and Cardon LR

    Nature genetics 2006;38;6;659-62

  • A haplotype map of the human genome.

    International HapMap Consortium

    Nature 2005;437;7063;1299-320

  • Haploview: analysis and visualization of LD and haplotype maps.

    Barrett JC, Fry B, Maller J and Daly MJ

    Bioinformatics (Oxford, England) 2005;21;2;263-5

Barrett, Jeffrey
Jeffrey's Timeline
2015

Appointed Founding Director of Open Targets

2008

Joined Sanger Institute

Postdoc with David Clayton on GWAS meta-analyses

2005

Moved to Oxford

2004

Fulfilled dream as Bostonian: saw Red Sox win World Series at Fenway Park

2003

Haploview software released

2002

Graduated from MIT with BS in physics

1997

First genomics job: correcting sequencing gel lane alignment