Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease.

Publication: Nature Communications

Emdin CA, Khera AV, Chaffin M, Klarin D, Natarajan P, Aragam K, et al.

24 April 2018

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Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

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

14 April 2018


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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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

Publication: Nature Genetics

Mahajan A, Wessel J, Willems SM, Zhao W, Robertson NR, Chu AY, et al.

9 April 2018

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Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Publication: Nature Genetics

Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, et al.

12 March 2018

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Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and Meta-analysis

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

30 January 2018


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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Mortality in dementia with Lewy bodies compared to Alzheimer’s dementia: a retrospective naturalistic cohort study

Publication: BMJ Open

Price A, Farooq R, Yuan J-M, Menon VB, Cardinal RN, O’Brien JT

3 November 2017


The researchers here aimed to use routine clinical data to investigate survival in dementia with Lewy bodies (DLB) compared with Alzheimer’s dementia (AD).

DLB is the second most common dementia subtype after AD, accounting for around 7% of dementia diagnoses in secondary care, though studies suggest that it is underdiagnosed by up to 50%.

Most previous studies of DLB have been based on select research cohorts, so little is known about the outcome of the disease in routine healthcare settings.

Working with Cambridgeshire & Peterborough NHS Foundation Trust, a mental health trust providing secondary mental health care in England, the researchers used samples from 251 DLB and 222 AD identified from an anonymised database, derived from electronic clinical case records across an 8-year period (2005-2012), with mortality data updated to May 2015.

Raw (uncorrected) median survival was 3.72 years for DLB and 6.95 years for AD. Controlling for age at diagnosis, comorbidity and antipsychotic prescribing the model predicted median survival for DLB was 3.3 years for males and 4.0 years for females, while median survival for AD was 6.7 years for males and 7.0 years for females.

The researchers concluded that survival from first presentation with cognitive impairment was markedly shorter in DLB compared with AD, independent of age, sex, physical comorbidity or antipsychotic prescribing.

This finding, in one of the largest clinical cohorts of DLB cases assembled to date, adds to existing evidence for poorer survival for DLB versus AD. There is an urgent need for further research to understand possible mechanisms accounting for this finding.

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Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

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

20 September 2017

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Clinical records anonymisation and text extraction (CRATE): an open-source software system

Publication: BMC Medical Informatics and Decision Making

Rudolf N Cardinal

26 April 2017


Electronic medical records contain information of value for research, but contain identifiable and often highly sensitive confidential information.

Patient-identifiable information cannot in general be shared outside clinical care teams without explicit consent, but anonymisation/de-identification allows research uses of clinical data without explicit consent.

This article presents CRATE (Clinical Records Anonymisation and Text Extraction), an open-source software system with separable functions: (1) it anonymises or de-identifies arbitrary relational databases, with sensitivity and precision similar to previous comparable systems; (2) it uses public secure cryptographic methods to map patient identifiers to research identifiers (pseudonyms); (3) it connects relational databases to external tools for natural language processing; (4) it provides a web front end for research and administrative functions; and (5) it supports a specific model through which patients may consent to be contacted about research.

Creation and management of a research database from sensitive clinical records with secure pseudonym generation, full-text indexing, and a consent-to-contact process is possible and practical using entirely free and open-source software.

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Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

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

12 April 2017

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The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

Publication: Cell

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.

17 November 2016

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