Malaria host candidate genes validated by association with current, recent and historic measures of transmission intensity.


Sepúlveda, N; Manjurano, A; Campino, SG; Lemnge, M; Lusingu, J; Olomi, R; Rockett, KA; Hubbart, C; Jeffreys, A; Rowlands, K; MalariaGen consortium, ; Clark, TG; Riley, EM; Drakeley, CJ; (2017) Malaria host candidate genes validated by association with current, recent and historic measures of transmission intensity. The Journal of infectious diseases. ISSN 0022-1899 DOI: 10.1093/infdis/jix250

Full text not available from this repository. (Request a copy)

Abstract

Human malaria susceptibility is determined by multiple genetic factors. It is however unclear which genetic variants remain important over time. Genetic associations of 175 high quality polymorphisms within several malaria candidate genes were examined in a sample of 8,096 individuals from northeast Tanzania using altitude, seroconversion rates and parasite rates as proxies of historical, recent and current malaria transmission intensity. A principal component (PC) analysis was used to derive two alternative measures of overall malaria propensity of a location across different time scales. Common red blood cell polymorphisms (i.e., HbS, G6PD and α-thalassaemia) were the only ones to be associated with all three measures of transmission intensity and the first PC. Moderate associations were found between some immune response genes (i.e., IL3 and IL13) and parasite rates, but these could not be reproduced using the alternative measures of malaria propensity. We have demonstrated the potential of using altitude and seroconversion rate as measures of malaria transmission capturing medium to long term time scales to detect genetic associations that are likely to persist over time. These measures also have the advantage of minimizing the deleterious effects of random factors affecting parasite rates on the respective association signals.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 28541483
Web of Science ID: 405951900008
URI: http://researchonline.lshtm.ac.uk/id/eprint/4363425

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
8Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item