Using genetic tools to understand the interactions between infection and nutrition
Sarah Atkinson
MBBS, BSc, MRCPCH, DTM&H, PhD, PGDipPID
Associate Professor and Honorary Consultant in Paediatrics and Paediatric Infectious Disease
Dr Sarah Atkinson is a Wellcome Trust Career Re-entry Fellow and Senior Lecturer in the Department of Paediatrics and at the KEMRI-Wellcome Trust Research Programme in Kilifi Kenya. Sarah completed her training in paediatrics and paediatric infectious disease in London, Newcastle and Oxford. Sarah first joined the Department of Paediatrics in 2007 as a Clinical Lecturer and has been based in Kenya since 2013. She is interested in using genetic epidemiology and other tools to understand the relationship between nutrition and infection in children.
Both micronutrient deficiencies and infectious diseases are common among children living in sub-Saharan Africa, but little is known about the effect that they have on each other. For example could malaria be causing iron deficiency, which affects >40% of children in Kilifi? We previously found that iron deficiency increases markedly over the malaria season in African children. The human hormone hepcidin controls iron regulation and prevents iron absorption and recycling. We found that hepcidin levels are unusually high in malaria even in asymptomatic infection suggesting that iron absorption may be impaired for prolonged periods in children who already have precarious iron intake. We are using genetic and epidemiological methods to investigate the impact of malaria on iron status. It is possible that elimination of malaria might also prevent an important cause of iron deficiency.
Nutritional status may also influence the risk of infection. The safety of iron supplementation is an important concern since pathogens require iron for their growth. I am using a Mendelian randomization (MR) to address the question of whether a child's iron status is causally related to their risk of malaria and/or bacterial infection. MR is an approach that utilizes the random allocation of genetic variants at conceptioin to investigate causality between an intermediate trait (iron status) and disease (infection). In order to identify genetic variants for MR, I am conducting the first genome-wide association study of iron status and hepcidin levels in African populations. Validated genetic variants will be taken forward to large MR case-control studies of severe malaria and bacteraemia using stored samples from the Kilifi Biobank and the MalariaGEN Consortium.