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Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference

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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. Timpson
Detailed 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.


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



Nature Communications, 2018, 9, Article number: 711

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