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Dr William Astle

Dr William Astle

University Lecturer in Haematological Genomics


Research Interests

I am interested in the application and development of statistical and epidemiological methods to understand haematological risk factors for cardiovascular diseases. My work covers genome-wide association studies, metabonomics, the analysis of NMR spectra and RNA-Seq data sets, and gene expression studies.

My current focus is on the analysis of the blood trait phenotypes measured in the UK Biobank and INTERVAL studies. These collaborations with colleagues from the CEU, Department of Haematology, and the Wellcome Trust Sanger Institute, had led to a 10-fold increase in the number of genetic loci known to modulate properties of the blood, and has identified reticulocyte count as a potential risk factor for coronary heart disease.

Keywords

blood cells ; cardiovascular disease ; biostatistics ; statistical and computational methods

Collaborators outside this directory

Key Publications

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, Mead D, Bouman H, Riveros-Mckay F, Kostadima MA, Lambourne JJ, Sivapalaratnam S, Downes K, Kundu K, Bomba L, Berentsen K, Bradley JR, Daugherty LC, Delaneau O, Freson K, Garner SF, Grassi L, Guerrero J, Haimel M, Janssen-Megens EM, Kaan A, Kamat M, Kim B, Mandoli A, Marchini J, Martens JH, Meacham S, Megy K, O'Connell J, Petersen R, Sharifi N, Sheard SM, Staley JR, Tuna S, van der Ent M, Walter K, Wang SY, Wheeler E, Wilder SP, Iotchkova V, Moore C, Sambrook J, Stunnenberg HG, Di Angelantonio E, Kaptoge S, Kuijpers TW, Carrillo-de-Santa-Pau E, Juan D, Rico D, Valencia A, Chen L, Ge B, Vasquez L, Kwan T, Garrido-Martín D, Watt S, Yang Y, Guigo R, Beck S, Paul DS, Pastinen T, Bujold D, Bourque G, Frontini M, Danesh J, Roberts DJ, Ouwehand WH, Butterworth AS, Soranzo N. Cell. 2016 Nov 17;167(5):1415-1429.e19.

Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia. Sivapalaratnam S, Westbury SK, Stephens JC, Greene D, Downes K, Kelly AM, Lentaigne C, Astle WJ, Huizinga EG, Nurden P, Papadia S, Peerlinck K, Penkett CJ, Perry DJ, Roughley C, Simeoni I, Stirrups K, Hart DP, Tait RC, Mumford AD; NIHR BioResource., Laffan MA, Freson K, Ouwehand WH, Kunishima S, Turro E. Blood. 2017 Jan 26;129(4):520-524.

Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps. Iotchkova V, Huang J, Morris JA, Jain D, Barbieri C, Walter K, Min JL, Chen L, Astle W, Cocca M, Deelen P, Elding H, Farmaki AE, Franklin CS, Franberg M, Gaunt TR, Hofman A, Jiang T, Kleber ME, Lachance G, Luan J, Malerba G, Matchan A, Mead D, Memari Y, Ntalla I, Panoutsopoulou K, Pazoki R, Perry JR, Rivadeneira F, Sabater-Lleal M, Sennblad B, Shin SY, Southam L, Traglia M, van Dijk F, van Leeuwen EM, Zaza G, Zhang W; UK10K Consortium., Amin N, Butterworth A, Chambers JC, Dedoussis G, Dehghan A, Franco OH, Franke L, Frontini M, Gambaro G, Gasparini P, Hamsten A, Issacs A, Kooner JS, Kooperberg C, Langenberg C, Marz W, Scott RA, Swertz MA, Toniolo D, Uitterlinden AG, van Duijn CM, Watkins H, Zeggini E, Maurano MT, Timpson NJ, Reiner AP, Auer PL, Soranzo N. Nat Genet. 2016 Nov;48(11):1303-1312.

A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss. Stritt S, Nurden P, Turro E, Greene D, Jansen SB, Westbury SK, Petersen R, Astle WJ, Marlin S, Bariana TK, Kostadima M, Lentaigne C, Maiwald S, Papadia S, Kelly AM, Stephens JC, Penkett CJ, Ashford S, Tuna S, Austin S, Bakchoul T, Collins P, Favier R, Lambert MP, Mathias M, Millar CM, Mapeta R, Perry DJ, Schulman S, Simeoni I, Thys C; BRIDGE-BPD Consortium., Gomez K, Erber WN, Stirrups K, Rendon A, Bradley JR, van Geet C, Raymond FL, Laffan MA, Nurden AT, Nieswandt B, Richardson S, Freson K, Ouwehand WH, Mumford AD. Blood. 2016 Jun 9;127(23):2903-14.

Bayesian deconvolution and quantification of metabolites in complex 1D NMR spectra using BATMAN. Hao J, Liebeke M, Astle W, De Iorio M, Bundy JG, Ebbels TM. Nat Protoc. 2014;9(6):1416-27.

Transcriptional diversity during lineage commitment of human blood progenitors. Chen L, Kostadima M, Martens JH, Canu G, Garcia SP, Turro E, Downes K, Macaulay IC, Bielczyk-Maczynska E, Coe S, Farrow S, Poudel P, Burden F, Jansen SB, Astle WJ, Attwood A, Bariana T, de Bono B, Breschi A, Chambers JC; BRIDGE Consortium., Choudry FA, Clarke L, Coupland P, van der Ent M, Erber WN, Jansen JH, Favier R, Fenech ME, Foad N, Freson K, van Geet C, Gomez K, Guigo R, Hampshire D, Kelly AM, Kerstens HH, Kooner JS, Laffan M, Lentaigne C, Labalette C, Martin T, Meacham S, Mumford A, Nürnberg S, Palumbo E, van der Reijden BA, Richardson D, Sammut SJ, Slodkowicz G, Tamuri AU, Vasquez L, Voss K, Watt S, Westbury S, Flicek P, Loos R, Goldman N, Bertone P, Read RJ, Richardson S, Cvejic A, Soranzo N, Ouwehand WH, Stunnenberg HG, Frontini M, Rendon A. Science. 2014 Sep 26;345(6204):1251033.

Flexible analysis of RNA-seq data using mixed effects models. Turro E, Astle WJ, Tavaré S. Bioinformatics. 2014 Jan 15;30(2):180-8.

The relationship between DXA-based and anthropometric measures of visceral fat and morbidity in women. Direk K, Cecelja M, Astle W, Chowienczyk P, Spector TD, Falchi M, Andrew T. BMC Cardiovasc Disord. 2013 Apr 3;13:25.

BATMAN--an R package for the automated quantification of metabolites from nuclear magnetic resonance spectra using a Bayesian model. Hao J, Astle W, De Iorio M, Ebbels TM. Bioinformatics. 2012 Aug 1;28(15):2088-90.

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