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

Laura J. Corbin, Vanessa Y. Tan, David A. Hughes, Kaitlin Wade, Dirk S. Paul, Katherine E. Tansey, Frances Butcher, Frank Dudbridge, Joanna M. M. Howson, Momodou W. Jallow, Catherine John, Nathalie Kingston, Cecilia M. Lindgren, Michael O’Donavan, Stephen O'Rahilly, Michael J. Owen, Colin Palmer, Ewan Pearson, Robert A. Scott, David van Heel & 11 others 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

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Article number711
Pages (from-to)1-11
Number of pages11
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 19 Feb 2018

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Keywords

  • Epidemiology
  • Genetics research
  • Medical genetics
  • Quantitative trait
  • Humans
  • Risk Factors
  • Genotype
  • United Kingdom
  • Genetic Variation
  • Phenotype
  • Molecular Epidemiology
  • Genome-Wide Association Study/methods
  • Causality

Cite this

Corbin, L. J., Tan, V. Y., Hughes, D. A., Wade, K., Paul, D. S., Tansey, K. E., ... Timpson, N. J. (2018). Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference. Nature Communications, 9(1), 1-11. [711]. https://doi.org/10.1038/s41467-018-03109-y
Corbin, Laura J. ; Tan, Vanessa Y. ; Hughes, David A. ; Wade, Kaitlin ; Paul, Dirk S. ; Tansey, Katherine E. ; Butcher, Frances ; Dudbridge, Frank ; Howson, Joanna M. M. ; Jallow, Momodou W. ; John, Catherine ; Kingston, Nathalie ; Lindgren, Cecilia M. ; O’Donavan, Michael ; O'Rahilly, Stephen ; Owen, Michael J. ; Palmer, Colin ; Pearson, Ewan ; Scott, Robert A. ; van Heel, David ; Whittaker, John ; Frayling, Tim ; Tobin, Martin D. ; Wain, Louise V. ; Smith, George Davey ; Evans, David M. ; Karpe, Fredrik ; McCarthy, Mark I. ; Danesh, John ; Franks, Paul W. ; Timpson, Nicholas J. / Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 1-11.
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abstract = "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.",
keywords = "Epidemiology, Genetics research, Medical genetics, Quantitative trait, Humans, Risk Factors, Genotype, United Kingdom, Genetic Variation, Phenotype, Molecular Epidemiology, Genome-Wide Association Study/methods, Causality",
author = "Corbin, {Laura J.} and Tan, {Vanessa Y.} and Hughes, {David A.} and Kaitlin Wade and Paul, {Dirk S.} and Tansey, {Katherine E.} and Frances Butcher and Frank Dudbridge and Howson, {Joanna M. M.} and Jallow, {Momodou W.} and Catherine John and Nathalie Kingston and Lindgren, {Cecilia M.} and Michael O’Donavan and Stephen O'Rahilly and Owen, {Michael J.} and Colin Palmer and Ewan Pearson and Scott, {Robert A.} and {van Heel}, David and John Whittaker and Tim Frayling and Tobin, {Martin D.} and Wain, {Louise V.} and Smith, {George Davey} and Evans, {David M.} and Fredrik Karpe and McCarthy, {Mark I.} and John Danesh and Franks, {Paul W.} and Timpson, {Nicholas J.}",
note = "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(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Avon Longitudinal Study of Parents and Children (ALSPAC): We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. ALSPAC mothers were genotyped using the Illumina human660W-quad array at Centre National de G{\'e}notypage (CNG) and genotypes were called with Illumina GenomeStudio. The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The authors also acknowledge Professor John Henderson for providing helpful comments on earlier drafts of the manuscript and Matthew Lee for proofreading the final submission.",
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month = "2",
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Corbin, LJ, Tan, VY, Hughes, DA, Wade, K, Paul, DS, Tansey, KE, Butcher, F, Dudbridge, F, Howson, JMM, Jallow, MW, John, C, Kingston, N, Lindgren, CM, O’Donavan, M, O'Rahilly, S, Owen, MJ, Palmer, C, Pearson, E, Scott, RA, van Heel, D, Whittaker, J, Frayling, T, Tobin, MD, Wain, LV, Smith, GD, Evans, DM, Karpe, F, McCarthy, MI, Danesh, J, Franks, PW & Timpson, NJ 2018, 'Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference', Nature Communications, vol. 9, no. 1, 711, pp. 1-11. https://doi.org/10.1038/s41467-018-03109-y

Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference. / Corbin, Laura J. ; Tan, Vanessa Y. ; Hughes, David A. ; Wade, Kaitlin; Paul, Dirk S. ; Tansey, Katherine E.; Butcher, Frances ; Dudbridge, Frank; Howson, Joanna M. M.; Jallow, Momodou W. ; John, Catherine ; Kingston, Nathalie ; Lindgren, Cecilia M.; O’Donavan, Michael ; O'Rahilly, Stephen; Owen, Michael J.; Palmer, Colin; Pearson, Ewan; Scott, Robert A.; van Heel, David ; Whittaker, John; Frayling, Tim; Tobin, Martin D.; Wain, Louise V.; Smith, George Davey; Evans, David M.; Karpe, Fredrik; McCarthy, Mark I.; Danesh, John; Franks, Paul W.; Timpson, Nicholas J. (Lead / Corresponding author).

In: Nature Communications, Vol. 9, No. 1, 711, 19.02.2018, p. 1-11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference

AU - Corbin, Laura J.

AU - Tan, Vanessa Y.

AU - Hughes, David A.

AU - Wade, Kaitlin

AU - Paul, Dirk S.

AU - Tansey, Katherine E.

AU - Butcher, Frances

AU - Dudbridge, Frank

AU - Howson, Joanna M. M.

AU - Jallow, Momodou W.

AU - John, Catherine

AU - Kingston, Nathalie

AU - Lindgren, Cecilia M.

AU - O’Donavan, Michael

AU - O'Rahilly, Stephen

AU - Owen, Michael J.

AU - Palmer, Colin

AU - Pearson, Ewan

AU - Scott, Robert A.

AU - van Heel, David

AU - Whittaker, John

AU - Frayling, Tim

AU - Tobin, Martin D.

AU - Wain, Louise V.

AU - Smith, George Davey

AU - Evans, David M.

AU - Karpe, Fredrik

AU - McCarthy, Mark I.

AU - Danesh, John

AU - Franks, Paul W.

AU - Timpson, Nicholas J.

N1 - 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(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Avon Longitudinal Study of Parents and Children (ALSPAC): We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. ALSPAC mothers were genotyped using the Illumina human660W-quad array at Centre National de Génotypage (CNG) and genotypes were called with Illumina GenomeStudio. The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The authors also acknowledge Professor John Henderson for providing helpful comments on earlier drafts of the manuscript and Matthew Lee for proofreading the final submission.

PY - 2018/2/19

Y1 - 2018/2/19

N2 - 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.

AB - 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.

KW - Epidemiology

KW - Genetics research

KW - Medical genetics

KW - Quantitative trait

KW - Humans

KW - Risk Factors

KW - Genotype

KW - United Kingdom

KW - Genetic Variation

KW - Phenotype

KW - Molecular Epidemiology

KW - Genome-Wide Association Study/methods

KW - Causality

U2 - 10.1038/s41467-018-03109-y

DO - 10.1038/s41467-018-03109-y

M3 - Article

VL - 9

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 711

ER -