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Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
journal contribution
posted on 2018-01-26, 10:51 authored by Laura J. Corbin, Vanessa Y. Tan, David A. Hughes, Kaitlin H. Wade, Dirk S. Paul, Katherine E. Tansey, Frances Butcher, Frank Dudbridge, Joanna M. Howson, Momodou W. Jallow, Catherine John, Nathalie Kingston, Cecilia M. Lindgren, Michael O’Donavan, Stephen O’Rahilly, Michael J. Owen, Colin N. A. Palmer, Ewan R. Pearson, Robert A. Scott, David A. van Heel, John Whittaker, Tim Frayling, Martin D. Tobin, Louise V. Wain, George Davey Smith, David M. Evans, Fredrik Karpe, Mark I. McCarthy, John Danesh, Paul W. Franks, Nicholas J. TimpsonDetailed phenotyping is required to deepen our understanding of the biological mechanisms
behind genetic associations. In addition, the impact of potentially modifiable risk factors on
disease requires analytical frameworks that allow causal inference. Here, we discuss the
characteristics of Recall by Genotype (RbG) as a study design aimed at addressing both these
needs. We describe two broad scenarios for the application of RbG: studies using single
variants and those using multiple variants. We consider the efficacy and practicality of the
RbG approach, provide a catalogue of UK-based resources for such studies and present an
online RbG study planner.
Funding
This work was supported by the Medical Research Council MC_UU_12013/3 (NJT, LJC, KHW, DAH) and MC_UU_12013/1 (GDS). NJT is a Wellcome Trust Investigator (202802/Z/16/Z) and works within the University of Bristol NIHR Biomedical Research Centre (BRC). NJT and VJT are supported by the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). The MRC/BHF Cardiovascular Epidemiology Unit is supported by the UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194) and NIHR Cambridge Biomedical Research Centre. DSP is supported by the BHF Cambridge Centre of Excellence (RE/13/6/30180) and the Wellcome Trust (105602/Z/14/Z). CML is supported by the Li Ka Shing Foundation and NIHR Oxford Biomedical Research Centre. Work undertaken by PWF related to this manuscript is supported by the European Research Council (ERC-2015-CoG-681742-NASCENT) and the Swedish Research Council (Distinguished Young Researcher Award in Medicine). The EXCEED study at the University of Leicester has been supported by the Medical Research Council (G0902313) and received partial support from NIHR; the views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The EXCEED study gratefully acknowledges the support of all participants and staff who have contributed to the study. LVW holds a GlaxoSmithKline/British Lung Foundation Chair in Respiratory Research. MDT holds a Wellcome Trust Investigator Award (WT 202849/Z/16/Z). CJ holds a Medical Research Council Clinical Research Training Fellowship (MR/P00167X/1). MMcC is a Wellcome Trust Senior Investigator and an NIHR Senior Investigator. Research support relevant to this manuscript comes from Wellcome Trust (090532, 098381, 106130), Medical Research Council (MR/L020149/1) and NIH (R01DK098032; U01DK105535). The research was supported by the National Institute for Health Research (NIHR) Oxford BRC. The views expressed are those of the author
History
Citation
Nature Communications, 2018, 9, Article number: 711Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health SciencesVersion
- VoR (Version of Record)
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Nature CommunicationsPublisher
Nature Publishing Groupeissn
2041-1723Acceptance date
2018-01-19Copyright date
2018Available date
2018-03-28Publisher DOI
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https://www.nature.com/articles/s41467-018-03109-yLanguage
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