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Dr Adam Butterworth

Research themes

Epidemiology:

Research Interests

Genetic determinants of cardiovascular disease and high-dimensional traits

Genetic discovery: My main focus is around the identification of genetic variation linked with coronary disease and related phenotypes using customised SNP arrays. Current efforts in this area include the 50,000-participant CardioMetabochip+ consortium and the 100,000 participant Exome+ consortium that are coordinated by us at Cardiovascular Epidemiology Unit (CEU).

Human genetics to inform therapeutics: By relating informative genetic variants to disease outcomes and phenotypes, inference can be made about the likely efficacy and safety profile of current and potential therapeutic agents. For example, we have highlighted the relationship of IL6R variants to risk of heart disease, raising the possibility of monoclonal antibodies being repurposed from inflammatory conditions to cardiovascular pathways. I work closely with large pharmaceutical companies to help discover and evaluate pathways of potential therapeutic interest.

EPIC-CVD: I am the Scientific Coordinator of the EPIC-Heart/EPIC-CVD study, which is a pan-European study of incident coronary disease and stroke including participants from 23 Centres across 10 European countries. This project has a wealth of genetic, biochemical and risk factor data, which are predominantly utilised for the study of gene-environment interaction, cardiovascular risk prediction, and genetic discovery.

Keywords

epidemiology ; epigenetics ; mendelian randomisation

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.

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Surendran P, Drenos F, Young R, ..., Danesh J, Wain LV, Butterworth AS, Howson JM, Munroe PB. Nat Genet. 2016 Oct;48(10):1151-61.

Parity, breastfeeding and risk of coronary heart disease: A pan-European case-cohort study. Peters SA, van der Schouw YT, Wood AM, Sweeting MJ, Moons KG, Weiderpass E, Arriola L, Benetou V, Boeing H, Bonnet F, Butt ST, Clavel-Chapelon F, Drake I, Gavrila D, Key TJ, Klinaki E, Krogh V, Kühn T, Lassale C, Masala G, Matullo G, Merritt M, Molina-Portillo E, Moreno-Iribas C, Nøst TH, Olsen A, Onland-Moret NC, Overvad K, Panico S, Redondo ML, Tjønneland A, Trichopoulou A, Tumino R, Turzanski-Fortner R, Tzoulaki I, Wennberg P, Winkvist A, Thompson SG, Di Angelantonio E, Riboli E, Wareham NJ, Danesh J, Butterworth AS. Eur J Prev Cardiol. 2016 Nov;23(16):1755-1765.

PhenoScanner: a database of human genotype-phenotype associations. Staley JR, Blackshaw J, Kamat MA, Ellis S, Surendran P, Sun BB, Paul DS, Freitag D, Burgess S, Danesh J, Young R, Butterworth AS. Bioinformatics. 2016 Oct 15;32(20):3207-3209.

A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Scott RA, Freitag DF, Li L, ..., Butterworth AS, Dupuis J, Easton DF, Eeles RA, Erdmann J, Franks PW, Frayling TM, Hansen T, Howson JM, Jørgensen T, Kooner J, Laakso M, Langenberg C, McCarthy MI, Pankow JS, Pedersen O, Riboli E, Rotter JI, Saleheen D, Samani NJ, Schunkert H, Vollenweider P, O'Rahilly S; CHARGE consortium.; CHD Exome+ Consortium.; CARDIOGRAM Exome Consortium., Deloukas P, Danesh J, Goodarzi MO, Kathiresan S, Meigs JB, Ehm MG, Wareham NJ, Waterworth DM. Sci Transl Med. 2016 Jun 1;8(341):341ra76.

Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder Aa, Alam DS, Di Angelantonio E, Abecasis G, Chowdhury R, Erdmann J, Nordestgaard BG, Nielsen SF, Tybjærg-Hansen A, Schmidt RF, Kuulasmaa K, Liu DJ, Perola M, Blankenberg S, Salomaa V, Männistö S, Amouyel P, Arveiler D, Ferrieres J, Müller-Nurasyid M, Ferrario M, Kee F, Willer CJ, Samani N, Schunkert H, Butterworth AS, Howson JM, Peloso GM, Stitziel NO, Danesh J, Kathiresan S, Rader DJ; CHD Exome+ Consortium.; CARDIoGRAM Exome Consortium.; Global Lipids Genetics Consortium. Science. 2016 Mar 11;351(6278):1166-71.

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease. Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators, Stitziel NO, Stirrups KE, Masca NG, Erdmann J, Ferrario PG, König IR, Weeke PE, Webb TR, Auer PL, Schick UM, Lu Y, Zhang H, Dube MP, Goel A, Farrall M, Peloso GM, Won HH, Do R, van Iperen E, Kanoni S, Kruppa J, Mahajan A, Scott RA, Willenberg C, Braund PS, van Capelleveen JC, Doney AS, Donnelly LA, Asselta R, Merlini PA, Duga S, Marziliano N, Denny JC, Shaffer CM, El-Mokhtari NE, Franke A, Gottesman O, Heilmann S, Hengstenberg C, Hoffman P, Holmen OL, Hveem K, Jansson JH, Jöckel KH, Kessler T, Kriebel J, Laugwitz KL, Marouli E, Martinelli N, McCarthy MI, Van Zuydam NR, Meisinger C, Esko T, Mihailov E, Escher SA, Alvar M, Moebus S, Morris AD, Müller-Nurasyid M, Nikpay M, Olivieri O, Lemieux Perreault LP, AlQarawi A, Robertson NR, Akinsanya KO, Reilly DF, Vogt TF, Yin W, Asselbergs FW, Kooperberg C, Jackson RD, Stahl E, Strauch K, Varga TV, Waldenberger M, Zeng L, Kraja AT, Liu C, Ehret GB, Newton-Cheh C, Chasman DI, Chowdhury R, Ferrario M, Ford I, Jukema JW, Kee F, Kuulasmaa K, Nordestgaard BG, Perola M, Saleheen D, Sattar N, Surendran P, Tregouet D, Young R, Howson JM, Butterworth AS, Danesh J, Ardissino D, Bottinger EP, Erbel R, Franks PW, Girelli D, Hall AS, Hovingh GK, Kastrati A, Lieb W, Meitinger T, Kraus WE, Shah SH, McPherson R, Orho-Melander M, Melander O, Metspalu A, Palmer CN, Peters A, Rader D, Reilly MP, Loos RJ, Reiner AP, Roden DM, Tardif JC, Thompson JR, Wareham NJ, Watkins H, Willer CJ, Kathiresan S, Deloukas P, Samani NJ, Schunkert H. N Engl J Med. 2016 Mar 24;374(12):1134-44.

Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study. Podmore C, Meidtner K, Schulze MB, Scott RA, Ramond A, Butterworth AS, Di Angelantonio E, Danesh J, Arriola L, Barricarte A, Boeing H, Clavel-Chapelon F, Cross AJ, Dahm CC, Fagherazzi G, Franks PW, Gavrila D, Grioni S, Gunter MJ, Gusto G, Jakszyn P, Katzke V, Key TJ, Kühn T, Mattiello A, Nilsson PM, Olsen A, Overvad K, Palli D, Quirós JR, Rolandsson O, Sacerdote C, Sánchez-Cantalejo E, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, van der A DL, van der Schouw YT, Feskens EJ, Forouhi NG, Sharp SJ, Riboli E, Langenberg C, Wareham NJ. Diabetes Care. 2016 Apr;39(4):572-81.

Information and Risk Modification Trial (INFORM): design of a randomised controlled trial of communicating different types of information about coronary heart disease risk, alongside lifestyle advice, to achieve change in health-related behaviour. Silarova B, Lucas J, Butterworth AS, Di Angelantonio E, Girling C, Lawrence K, Mackintosh S, Moore C, Payne RA, Sharp SJ, Shefer G, Tolkien Z, Usher-Smith J, Walker M, Danesh J, Griffin S. BMC Public Health. 2015 Sep 7;15:868.

Beyond Mendelian randomization: how to interpret evidence of shared genetic predictors. Burgess S, Butterworth AS, Thompson JR. J Clin Epidemiol. 2016 Jan;69:208-16.

Association of Cardiometabolic Multimorbidity With Mortality. Emerging Risk Factors Collaboration., Di Angelantonio E, Kaptoge S, Wormser D, Willeit P, Butterworth AS, Bansal N, O'Keeffe LM, Gao P, Wood AM, Burgess S, Freitag DF, Pennells L, Peters SA, Hart CL, Håheim LL, Gillum RF, Nordestgaard BG, Psaty BM, Yeap BB, Knuiman MW, Nietert PJ, Kauhanen J, Salonen JT, Kuller LH, Simons LA, van der Schouw YT, Barrett-Connor E, Selmer R, Crespo CJ, Rodriguez B, Verschuren WM, Salomaa V, Svärdsudd K, van der Harst P, Björkelund C, Wilhelmsen L, Wallace RB, Brenner H, Amouyel P, Barr EL, Iso H, Onat A, Trevisan M, D'Agostino RB Sr, Cooper C, Kavousi M, Welin L, Roussel R, Hu FB, Sato S, Davidson KW, Howard BV, Leening MJ, Rosengren A, Dörr M, Deeg DJ, Kiechl S, Stehouwer CD, Nissinen A, Giampaoli S, Donfrancesco C, Kromhout D, Price JF, Peters A, Meade TW, Casiglia E, Lawlor DA, Gallacher J, Nagel D, Franco OH, Assmann G, Dagenais GR, Jukema JW, Sundström J, Woodward M, Brunner EJ, Khaw KT, Wareham NJ, Whitsel EA, Njølstad I, Hedblad B, Wassertheil-Smoller S, Engström G, Rosamond WD, Selvin E, Sattar N, Thompson SG, Danesh J. JAMA. 2015 Jul 7;314(1):52-60.

The Bangladesh Risk of Acute Vascular Events (BRAVE) Study: objectives and design. Chowdhury R, Alam DS, Fakir II, Adnan SD, Naheed A, Tasmin I, Monower MM, Hossain F, Hossain FM, Rahman MM, Afrin S, Roy AK, Akter M, Sume SA, Biswas AK, Pennells L, Surendran P, Young RD, Spackman SA, Hasan K, Harshfield E, Sheikh N, Houghton R, Saleheen D, Howson JM, Butterworth AS; Cardiology Research Group., Raqib R, Majumder AA, Danesh J, Di Angelantonio E. Eur J Epidemiol. 2015 Jul;30(7):577-87.

Full list of publications can be found here.

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