Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision.

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 th

SUBMITTER: Watson JA 

PROVIDER: S-EPMC8315799 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature