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Dr Adam Butterworth

Research themes

Population Sciences:

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

Full list of publications can be found here.

Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis. Burgess S, Ference BA, Staley JR, Freitag DF, ..., Butterworth AS, Danesh J; European Prospective Investigation Into Cancer and Nutrition–Cardiovascular Disease (EPIC-CVD) Consortium. JAMA Cardiol. 2018 Jun 20. doi: 10.1001/jamacardio.2018.1470. [Epub ahead of print]

Genomic atlas of the human plasma proteome. Sun BB, Maranville JC, Peters JE, Stacey D, Staley JR, Blackshaw J, Burgess S, Jiang T, Paige E, Surendran P, Oliver-Williams C, Kamat MA, Prins BP, Wilcox SK, Zimmerman ES, Chi A, Bansal N, Spain SL, Wood AM, Morrell NW, Bradley JR, Janjic N, Roberts DJ, Ouwehand WH, Todd JA, Soranzo N, Suhre K, Paul DS, Fox CS, Plenge RM, Danesh J, Runz H, Butterworth AS. Nature. 2018 Jun;558(7708):73-79.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study. Ricci C, Wood A, Muller D, ..., Butterworth AS, Riboli E, Wareham NJ, Danesh J, Ferrari P. BMJ. 2018 May 29;361:k934.

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study. Lane WJ, Westhoff CM, Gleadall NS, Aguad M, Smeland-Wagman R, Vege S, Simmons DP, Mah HH, Lebo MS, Walter K, Soranzo N, Di Angelantonio E, Danesh J, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Kaufman RM, Rehm HL, Silberstein LE, Green RC; MedSeq Project. Lancet Haematol. 2018 Jun;5(6):e241-e251.

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Wood AM, Kaptoge S, Butterworth AS, ..., Di Angelantonio E, Danesh J; Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group. Lancet. 2018 Apr 14;391(10129):1513-1523.

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese AK, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HHH, Ago T, Almgren P, Amouyel P, Ay H, Bartz TM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD Jr, Butterworth AS, ..., MEGASTROKE Consortium. Nat Genet. 2018 Apr;50(4):524-537.

Exome-wide association study of plasma lipids in >300,000 individuals. Liu DJ, Peloso GM, Yu H, Butterworth AS, ..., Charge Diabetes Working Group; EPIC-InterAct Consortium; EPIC-CVD Consortium; GOLD Consortium; VA Million Veteran Program, Howson JMM, Danesh J, McCarthy MI, Cowan CA, Abecasis G, Deloukas P, Musunuru K, Willer CJ, Kathiresan S. Nat Genet. 2017 Dec;49(12):1758-1766.

New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. Kraja AT, Cook JP, Warren HR, Surendran P, ..., Butterworth AS, Danesh J, Asselbergs FW, Wain LV, Ehret GB, Chasman DI, Caulfield MJ, Elliott P, Lindgren CM, Levy D, Newton-Cheh C, Munroe PB, Howson JMM; CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group†. Circ Cardiovasc Genet. 2017 Oct;10(5).

Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis. Lassale C, Tzoulaki I, Moons KGM, Sweeting M, ..., Di Angelantonio E, Riboli E, Wareham NJ, Danesh J, Butterworth AS. Eur Heart J. 2018 Feb 1;39(5):397-406.

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease. Zhao W, Rasheed A, Tikkanen E, Lee JJ, Butterworth AS, Howson JMM, ..., Rader DJ, Danesh J, Voight BF, Saleheen D. Nat Genet. 2017 Oct;49(10):1450-1457.

Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk. Ference BA, Kastelein JJP, Ginsberg HN, Chapman MJ, Nicholls SJ, Ray KK, Packard CJ, Laufs U, Brook RD, Oliver-Williams C, Butterworth AS, Danesh J, Smith GD, Catapano AL, Sabatine MS. JAMA. 2017 Sep 12;318(10):947-956.

Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nelson CP, Goel A, Butterworth AS, ..., EPIC-CVD Consortium; CARDIoGRAMplusC4D; UK Biobank CardioMetabolic Consortium CHD working group, Schunkert H, Farrall M, Danesh J, Samani NJ, Watkins H, Deloukas P. Nat Genet. 2017 Sep;49(9):1385-1391.

Platelet function is modified by common sequence variation in megakaryocyte super enhancers. Petersen R, Lambourne JJ, Javierre BM, ..., Butterworth AS, Heemskerk JW, Turro E, Spivakov M, Ouwehand WH, Astle WJ, Downes K, Kostadima M, Frontini M. Nat Commun. 2017 Jul 13;8:16058.

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease. Astle WJ, Elding H, Jiang T, ..., Ouwehand WH, Butterworth AS, Soranzo N. Cell. 2016 Nov 17;167(5):1415-1429.e19.

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Howson JMM, Zhao W, Barnes DR, ..., Assimes TL, Danesh J, Butterworth AS, Saleheen D. Nat Genet. 2017 Jul;49(7):1113-1119.

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, ..., 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, ..., 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, ..., 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, ..., 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, ..., 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.

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