Publications

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Publication: Journal of the American College of Cardiology

Michael Inouye, Gad Abraham, Christopher P. Nelson, Angela M. Wood, Michael J. Sweeting, Frank Dudbridge, Florence Y. Lai, Stephen Kaptoge, Marta Brozynska, Tingting Wang, Shu Ye, Thomas R. Webb, Martin K. Rutter, Ioanna Tzoulaki,Riyaz S. Patel, Ruth J.F. Loos, Bernard Keavney, Harry Hemingway, John Thompson, Hugh Watkins, Panos Deloukas,Emanuele Di Angelantonio, Adam S. Butterworth, John Danesh, Nilesh J. Samani


Summary:

Genetic factors have long been known to be major contributors of someone’s risk of developing coronary heart disease – the leading cause of heart attacks. Currently to identify those at risk doctors use scores based on lifestyle and clinical conditions associated with coronary heart disease such as cholesterol level, blood pressure, diabetes and smoking. But these scores are imprecise, age-dependent and miss a large proportion of people who appear ‘healthy’, but will still develop the disease.

The ‘big-data’ GRS technique takes into account 1.7 million genetic variants in a person’s DNA to calculate their underlying genetic risk for coronary heart disease.

The team analysed genomic data of nearly half a million people from the UK Biobank research project aged between 40-69 years. This included over 22,000 people who had coronary heart disease.

The GRS was better at predicting someone’s risk of developing heart disease than each of the classic risk factors for coronary heart disease alone. The ability of the GRS to predict coronary heart disease was also largely independent of these known risk factors. This showed that the genes which increase the risk of coronary heart disease don’t simply work by elevating blood pressure or cholesterol, for example.

People with a genomic risk score in the top 20 per cent of the population were over four-times more likely to develop coronary heart disease than someone with a genomic risk score in the bottom 20 per cent. Read the full press release

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Publication: The Lancet

Michael J Sweeting, Katya L Masconi, PhD, Edmund Jones, PhD, Pinar Ulug, PhD, Matthew J Glover, MSc, Prof Jonathan A Michaels, MChir, Prof Matthew J Bown, MD, Prof Janet T Powell, MD, Prof Simon G Thompson, DSc


Summary:

The NHS introduced ultrasound screening in men aged 65 and over in 2009 to detect and treat the condition – which arises when the main blood vessel swells in the abdomen, and is symptomless until the point of rupture. Since the launch, the programme has been successfully screening and identifying men at risk of an AAA.

Researchers wanted to see if UK women – who are less likely to have AAAs – could also benefit from a similar screening programme. Read the full press release here

 

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Publication: The Lancet

Angela M Wood PhD, P, Stephen Kaptoge, PhD, Adam S Butterworth, PhD, Peter Willeit, MD, Samantha Warnakula, PhD, Thomas Bolton, MMath, Ellie Paige, PhD, Dirk S Paul, PhD, Michael Sweeting, PhD, Stephen Burgess, PhD, Steven Bell, PhD, William Astle, PhD, David Stevens, MSc, Albert Koulman, PhD, Randi M Selmer, PhD, Prof W M Monique Verschuren, PhD, Prof Shinichi Sato, MD, Prof Inger Njølstad, MD, Prof Mark Woodward, PhD, Prof Veikko Salomaa, MD, Prof Børge G Nordestgaard, MD, Prof Bu B Yeap, MBBS, Prof Astrid Fletcher, PhD, Prof Olle Melander, MD, Prof Lewis H Kuller, MD, Beverley Balkau, PhD, Prof Michael Marmot, FMedSci, Prof Wolfgang Koenig, MD, Prof Edoardo Casiglia, MD, Prof Cyrus Cooper, FMedSci, Volker Arndt, MD, Prof Oscar H Franco, MD, Patrik Wennberg, MD, Prof John Gallacher, PhD, Agustín Gómez de la Cámara, MD, Prof Henry Völzke, MD, Christina C Dahm, PhD, Caroline E Dale, PhD, Manuela M Bergmann, PhD, Carlos J Crespo, PhD, Prof Yvonne T van der Schouw, PhD, Prof Rudolf Kaaks, MD, Leon A Simons, MD, Pagona Lagiou, MD, Josje D Schoufour, PhD, Jolanda M A Boer, PhD, Prof Timothy J Key, DPhil, Beatriz Rodriguez, MD, Conchi Moreno-Iribas, PhD, Karina W Davidson, PhD, James O Taylor, MD, Carlotta Sacerdote, PhD, Prof Robert B Wallace, MD, J Ramon Quiros, MD, Prof Rosario Tumino, MD, Dan G Blazer II, MD, Prof Allan Linneberg, MD, Makoto Daimon, MD, Salvatore Panico, MD, Barbara Howard, PhD, Guri Skeie, PhD, Prof Timo Strandberg, MD, Prof Elisabete Weiderpass, PhD, Prof Paul J Nietert, PhD, Prof Bruce M Psaty, MD, Prof Daan Kromhout, PhD, Elena Salamanca-Fernandez, MSc, Prof Stefan Kiechl, MD, Prof Harlan M Krumholz, MD, Sara Grioni, BSc, Domenico Palli, MD, José M Huerta, PhD, Prof Jackie Price, MD, Prof Johan Sundström, MD, Larraitz Arriola, MD, Prof Hisatomi Arima, MD, Ruth C Travis, DPhil, Prof Demosthenes B Panagiotakos, PhD, Anna Karakatsani, MD, Prof Antonia Trichopoulou, MD, Tilman Kühn, PhD, Prof Diederick E Grobbee, MD, Elizabeth Barrett-Connor, MD, Natasja van Schoor, MD, Prof Heiner Boeing, PhD, Prof Kim Overvad, MD, Prof Jussi Kauhanen, MD, Prof Nick Wareham, MD, Claudia Langenberg, MD, Prof Nita Forouhi, PhD, Maria Wennberg, PhD, Prof Jean-Pierre Després, DPhil, Prof Mary Cushman, MD, Jackie A Cooper, MSc, Prof Carlos J Rodriguez, MD, Masaru Sakurai, MD, Jonathan E Shaw, PhD, Prof Matthew Knuiman, PhD, Trudy Voortman, PhD, Prof Christa Meisinger, MD, Anne Tjønneland, MD, Prof Hermann Brenner, MD, Luigi Palmieri, PhD, Jean Dallongeville, MD, Prof Eric J Brunner, PhD, Prof Gerd Assmann, MD, Maurizio Trevisan, MD, Richard F Gillum, MD, Prof Ian Ford, PhD, Prof Naveed Sattar, FMedSci, Mariana Lazo, MD, Prof Simon G Thompson, FMedSci, Pietro Ferrari, PhD, Prof David A Leon, PhD, Prof George Davey Smith, MD, Prof Richard Peto, FRS, Prof Rod Jackson, PhD, Prof Emily Banks, PhD, Emanuele Di Angelantonio, MD, Prof John Danesh,


Summary:

Regularly drinking more than the recommended UK guidelines for alcohol could take years off your life, according to new research from the University of Cambridge. The study shows that drinking more alcohol is associated with a higher risk of stroke, fatal aneurysm, heart failure and death.

The authors say their findings challenge the widely held belief that moderate drinking is beneficial to cardiovascular health, and support the UK’s recently lowered guidelines. The study compared the health and drinking habits of over 600,000 people in 19 countries worldwide and controlled for age, smoking, history of diabetes, level of education and occupation.

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Publication: Annals

Linda M. O’Keeffe, PhD; Anna Ramond, DPharm; Clare Oliver-Williams, PhD; Peter Willeit, MD; Ellie Paige, PhD; Patrick Trotter, MBChB; Jonathan Evans, MBChB; Jonas Wadström, MD; Michael Nicholson, MD; Dave Collett, PhD; Emanuele Di Angelantonio, MD


Summary:

Living kidney donors are not at increased risk for some health outcomes previously of concern, but do seem at risk for worse blood pressure and kidney function than nondonors. In addition, female donors seem to be at increased risk for preeclampsia.

A team lead by researchers reviewed 52 published studies comprising more than 100,000 living kidney donors and more than 110,000 nondonors to assess the mid- and long-term health risks associated with living kidney donation in adults.

The data showed that kidney donors had higher diastolic blood pressure, poorer renal function, and higher risk for ESRD than nondonors. Female donors had an almost two-fold higher risk than nondonors for pregnancy-related complications, such as preeclampsia.

There was no evidence that living kidney donors had higher risk for mortality, cardiovascular disease, or type 2 diabetes, or reduced quality of life.

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Publication: The Lancet

Emanuele Di Angelantonio, Prof Simon G Thompson, Stephen Kaptoge, Carmel Moore, Matthew Walker, Prof Jane Armitage, Prof Willem H Ouwehand, Prof David J Roberts, Prof John Danesh

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Publication: Nature

Danish Saleheen, Pradeep Natarajan, Irina M. Armean, Wei Zhao, Asif Rasheed, Sumeet A. Khetarpal, Hong-Hee Won, Konrad J. Karczewski, Anne H. O’Donnell-Luria, Kaitlin E. Samocha, Benjamin Weisburd, Namrata Gupta, Mozzam Zaidi, Maria Samuel, Atif Imran, Shahid Abbas, Faisal Majeed, Madiha Ishaq, Saba Akhtar, Kevin Trindade, Megan Mucksavage, Nadeem Qamar, Khan Shah Zaman, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Nadeem Hayyat Mallick, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Khalid Mahmood, Naveeduddin Ahmed,   Ron Do, Ronald M. Krauss, Daniel G. MacArthur, Stacey Gabriel,  Eric S. Lander, Mark J. Daly, Philippe Frossard, John Danesh, Daniel J. Rader  & Sekar Kathiresan

Online April 12, 2017. DOI: 10.1038/nature22034

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Publication: Cell 2016

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.

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Publication: Lancet 2016

Di Angelantonio E, Bhupathiraji SN, Wormser D, Gao P, Kaptoget S, Berrington de Gonzalez A, Cairns BJ, Huxley R, Jackson CL, Joshy G, Lewington S, Manson JE, Murphy N, Patel AV, Samet JM, Woodward M, Zheng W, Zhou M, Bansal N, Barricarte A, Carter B, Cerhan JR, Collins R, Davey Smith G, Franco OH, Green J, Halsey J, Hildebrand JS, Jung KJ, Korda RJ, McLerran DF, Moore SC, O’Keeffe LM, Paige E, Ramond A, Reeves GK, Rolland B, Sacerdote C, Sattar N, Sofanopoulou E,Stevens J, Thun M, Ueshima H, Yang L, Duk Yun Y, Willeit P, Banks E, Beral V, Chen Z, Gapstur SM, Gunter MJ, Hartge P, Jee SH, Lam T-H, Peto R, Potter JD, Willet WC, Thompson SG, Danesh J*, Hu FB*.

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Publication: Lancet Diabetes Endocrinol 2016

Willeit P, Kaptoge S, Welsh P, Butterworth AS, Chowdury R, Spackman S, Pennells L,Gao P, Burgess S, Freitag DF, Sweeting M, Wood AM, Cook NR, Judd S, Trompet S, Nambi V, Hecht Olsen M, Everett BM, Kee F, Ärnlöv J, Salomaa V, Levy D, Kauhanen J, Laukkanen JA, Kavousi M, Ninomiya T, Casas J-P, Daniels LB, Lind L, Kistorp CN, Rosenberg J, Mueller T, Rubattu S, Panagiotakos DB, Franco OH, de Lemos JA, Luchner A, St Marien K, Kizer JR, Kiechl S, Salonen JT, Wannamethee SG, Nordestgaard BG, Anderson J, Jørgensen T, Melander O, Ballantyne CM, DeFilippi C, Ridker PM, Cushman M, Rosamond WD, Thompson SG, Gudnason V, Sattar N, Danesh J, Di Angelantonio E.

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Publication: Nat Genet 2016

Surendran P, Drenos F, Young R, Warren H, Cook JP, Manning AK, Grarup N, Sim X, Barnes DR, Witkowska K, Staley JR, Tragante V, Tukiainen T, Yaghootkar H, Masca N, Freitag DF, Ferreira T, Giannakopoulou O, Tinker A, Harakalova M, Mihailov E, Liu C, Kraja AT, Nielsen SF, Rasheed A, Samuel M, Zhao W, Bonnycastle LL, Jackson AU, Narisu N, Swift AJ, Southam L, Marten J, Huyghe JR, Stančáková A, Fava C, Ohlsson T, Matchan A, Stirrups KE, Bork-Jensen J, Gjesing AP, Kontto J, Perola M, Shaw-Hawkins S, Havulinna AS, Zhang H, Donnelly LA, Groves CJ, Rayner NW, Neville MJ, Robertson NR, Yiorkas AM, Herzig KH, Kajantie E, Zhang W, Willems SM, Lannfelt L, Malerba G, Soranzo N, Trabetti E, Verweij N, Evangelou E, Moayyeri A, Vergnaud AC, Nelson CP, Poveda A, Varga TV, Caslake M, de Craen AJ, Trompet S, Luan J, Scott RA, Harris SE, Liewald DC, Marioni R, Menni C, Farmaki AE, Hallmans G, Renström F, Huffman JE, Hassinen M, Burgess S, Vasan RS, Felix JF; CHARGE-Heart Failure Consortium, Uria-Nickelsen M, Malarstig A, Reilly DF, Hoek M, Vogt TF, Lin H, Lieb W; EchoGen Consortium, Traylor M, Markus HS; METASTROKE Consortium, Highland HM, Justice AE, Marouli E; GIANT Consortium, Lindström J, Uusitupa M, Komulainen P, Lakka TA, Rauramaa R, Polasek O, Rudan I, Rolandsson O, Franks PW, Dedoussis G, Spector TD; EPIC-InterAct Consortium, Jousilahti P, Männistö S, Deary IJ, Starr JM, Langenberg C, Wareham NJ, Brown MJ, Dominiczak AF, Connell JM, Jukema JW, Sattar N, Ford I, Packard CJ, Esko T, Mägi R, Metspalu A, de Boer RA, van der Meer P, van der Harst P; Lifelines Cohort Study, Gambaro G, Ingelsson E, Lind L, de Bakker PI, Numans ME, Brandslund I, Christensen C, Petersen ER, Korpi-Hyövälti E, Oksa H, Chambers JC, Kooner JS, Blakemore AI, Franks S, Jarvelin MR, Husemoen LL, Linneberg A, Skaaby T, Thuesen B, Karpe F, Tuomilehto J, Doney AS, Morris AD, Palmer CN, Holmen OL, Hveem K, Willer CJ, Tuomi T, Groop L, Käräjämäki A, Palotie A, Ripatti S, Salomaa V, Alam DS, Majumder AA, Di Angelantonio E, Chowdhury R, McCarthy MI, Poulter N, Stanton AV, Sever P, Amouyel P, Arveiler D, Blankenberg S, Ferrières J, Kee F, Kuulasmaa K, Müller-Nurasyid M, Veronesi G, Virtamo J, Deloukas P; Wellcome Trust Case Control Consortium, Elliott P; Understanding Society Scientific Group, Zeggini E, Kathiresan S, Melander O, Kuusisto J, Laakso M, Padmanabhan S, Porteous DJ, Hayward C, Scotland G, Collins FS, Mohlke KL, Hansen T, Pedersen O, Boehnke M, Stringham HM; EPIC-CVD Consortium, Frossard P, Newton-Cheh C; CHARGE+ Exome Chip Blood Pressure Consortium, Tobin MD, Nordestgaard BG; T2D-GENES Consortium; GoT2DGenes Consortium; ExomeBP Consortium; CHD Exome+ Consortium, Caulfield MJ, Mahajan A, Morris AP, Tomaszewski M, Samani NJ, Saleheen D, Asselbergs FW, Lindgren CM, Danesh J, Wain LV, Butterworth AS, Howson JM, Munroe PB.

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Publication: Science 2016

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.

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