Repository logo
  • Log In
    Log in via Symplectic to deposit your publication(s).
Repository logo
  • Communities & Collections
  • Research Outputs
  • Statistics
  • Log In
    Log in via Symplectic to deposit your publication(s).
  1. Home
  2. Faculty of Medicine
  3. School of Public Health
  4. Department of Infectious Diseases
  5. Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.
 
  • Details
Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.
File(s)
elife-69698-v2.pdf (8.26 MB)
Published version
Author(s)
Watson, James A
Ndila, Carolyne M
Uyoga, Sophie
Macharia, Alexander
Nyutu, Gideon
more
Type
Journal Article
Abstract
Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis, is imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model we re-analysed clinical and genetic data from 2,220 Kenyan children with clinically defined severe malaria and 3,940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.
Date Issued
2021-07-06
Date Acceptance
2021-06-22
Citation
eLife, 2021, 10, pp.1-39
URI
http://hdl.handle.net/10044/1/90622
URL
https://elifesciences.org/articles/69698
DOI
https://www.dx.doi.org/10.7554/eLife.69698
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Start Page
1
End Page
39
Journal / Book Title
eLife
Volume
10
Copyright Statement
© 2021 Watson et al. This
article is distributed under the
terms of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.
License URL
http://creativecommons.org/licenses/by/4.0/
Sponsor
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34225842
PII: 69698
Grant Number
202800/Z/16/Z
Subjects
epidemiology
genetics
genomics
global health
human
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2021-07-06
About
Spiral Depositing with Spiral Publishing with Spiral Symplectic
Contact us
Open access team Report an issue
Other Services
Scholarly Communications Library Services
logo

Imperial College London

South Kensington Campus

London SW7 2AZ, UK

tel: +44 (0)20 7589 5111

Accessibility Modern slavery statement Cookie Policy

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science

  • Cookie settings
  • Privacy policy
  • End User Agreement
  • Send Feedback