Watson, JA;
Ndila, CM;
Uyoga, S;
Macharia, A;
Nyutu, G;
Mohammed, S;
Ngetsa, C;
... White, NJ; + view all
(2021)
Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.
eLife
, 10
, Article e69698. 10.7554/eLife.69698.
Preview |
Text
Watson J improving statistical power malaria genotype studies eLife 2021.pdf - Published Version Download (8MB) | Preview |
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 are 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 2220 Kenyan children with clinically defined severe malaria and 3940 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.
Type: | Article |
---|---|
Title: | Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.7554/eLife.69698 |
Publisher version: | https://doi.org/10.7554/eLife.69698 |
Language: | English |
Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Biology, Life Sciences & Biomedicine - Other Topics, SEVERE FALCIPARUM-MALARIA, SICKLE-CELL-DISEASE, AFRICAN CHILDREN, CEREBRAL MALARIA, CASE DEFINITIONS, QUININE, ARTESUNATE, TRIAL |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
URI: | https://discovery.ucl.ac.uk/id/eprint/10133257 |
Archive Staff Only
View Item |