Imperial College London
Alternate

Claire L. Shovlin PhD FRCP

Faculty of Medicine, National Heart & Lung Institute

Professor of Practice (Clinical and Molecular Medicine)
 
 
 
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Contact

 

c.shovlin Website

 
 
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Location

 

534Block L Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Joyce:2021:10.1101/2021.08.28.21262560,
author = {Joyce, KE and Onabanjo, E and Brownlow, S and Nur, F and Olupona, KO and Fakayode, K and Sroya, M and Thomas, G and Ferguson, T and Redhead, J and Millar, CM and Cooper, N and Layton, DM and Boardman-Pretty, F and Caulfield, MJ and Shovlin, CL},
doi = {10.1101/2021.08.28.21262560},
publisher = {Cold Spring Harbor Laboratory},
title = {High definition analyses of single cohort, whole genome sequencing data provides a direct route to defining sub-phenotypes and personalising medicine},
url = {http://dx.doi.org/10.1101/2021.08.28.21262560},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Possession of a clinical or molecular disease label alters the context in which life-course events operate, but rarely explains the phenotypic variability observed by clinicians. Whole genome sequencing of unselected endothelial vasculopathy patients demonstrated more than a third had rare, likely deleterious variants in clinically-relevant genes unrelated to their vasculopathy (1 in 10 within platelet genes; 1 in 8 within coagulation genes; and 1 in 4 within erythrocyte hemolytic genes). High erythrocyte membrane variant rates paralleled genomic damage and prevalence indices in the general population. In blinded analyses, patients with greater hemorrhagic severity that had been attributed solely to their vasculopathy had more deleterious variants in platelet (Spearman ρ=0.25, p=0.008) and coagulation (Spearman ρ=0.21, p=0.024) genes. We conclude that rare diseases can provide insights for medicine beyond their primary pathophysiology, and propose a framework based on rare variants to inform interpretative approaches to accelerate clinical impact from whole genome sequencing.
AU  - Joyce,KE
AU  - Onabanjo,E
AU  - Brownlow,S
AU  - Nur,F
AU  - Olupona,KO
AU  - Fakayode,K
AU  - Sroya,M
AU  - Thomas,G
AU  - Ferguson,T
AU  - Redhead,J
AU  - Millar,CM
AU  - Cooper,N
AU  - Layton,DM
AU  - Boardman-Pretty,F
AU  - Caulfield,MJ
AU  - Shovlin,CL
DO  - 10.1101/2021.08.28.21262560
PB  - Cold Spring Harbor Laboratory
PY  - 2021///
TI  - High definition analyses of single cohort, whole genome sequencing data provides a direct route to defining sub-phenotypes and personalising medicine
UR  - http://dx.doi.org/10.1101/2021.08.28.21262560
UR  - https://www.medrxiv.org/content/10.1101/2021.08.28.21262560v1
UR  - http://hdl.handle.net/10044/1/92928
ER  -
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