Dataset Information

Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania.

ABSTRACT: The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as ~23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.

SUBMITTER: Malaria Genomic Epidemiology Network

PROVIDER: S-EPMC6914791 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania.

Nature communications 20191216 1

The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around ...[more]

PMID: 31844061

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Project description:BackgroundMalaria and visceral leishmaniasis (VL) co-infection can occur due to the overlapping geographical distributions of these diseases; however, only limited data of this co-infection have been reported and reviewed. This study aimed to explore the pooled prevalence and characteristics of this co-infection using a systematic review approach.MethodsThe PubMed, Web of Science and Scopus databases were searched for relevant studies. The quality of these studies was assessed in accordance with strengthening the reporting of observational studies in epidemiology (STROBE) guidelines. The numbers of individuals co-infected with Plasmodium and VL and the total numbers of individuals with VL were used to estimate the pooled prevalence using random-effects models. Differences in age, sex and the presence of anemia and malnutrition on admission were compared between co-infected individuals and individuals with VL using a random-effects model; the results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity among the included studies was assessed and quantified using Cochrane Q and I2 statistics.ResultsOf the 3075 studies identified, 12 met the eligibility criteria and were included in this systematic review. The pooled prevalence of Plasmodium infection among the 6453 individuals with VL was 13%, with substantial heterogeneity of the data (95% CI 7-18%, I2 97.9%). Subgroup analysis demonstrated that the highest prevalence of co-infection occurred in African countries, whereas the lowest prevalence occurred in Asian countries. Patients aged < 5 years had higher odds of having co-infection than having VL (co-infection, n = 202; VL, n = 410) (OR 1.66, 95% CI 1.37-2.01, I2 0%; P < 0.0001), whereas patients aged 20-29 years had lower odds of having co-infection than having VL (co-infection, n = 170; VL, n = 699) (OR 0.75, 95% CI 0.60-0.93, I2 18%; P = 0.01). Male patients had equivalent odds of having co-infection and having VL (co-infection, n = 525; VL, n = 2232) (OR 0.92, 95% CI 0.078-1.08, I2 0%; P = 0.29). Patients with co-infection had lower odds of having anemia at admission than those with VL (co-infection, n = 902; VL, n = 2939) (OR 0.64, 95% CI 0.44-0.93, I2 0%; P = 0.02). No difference in malnutrition at admission was found in the meta-analysis.ConclusionsThe prevalence of malaria co-infection among individuals with VL was heterogeneous and ranged from 7 to 18%, depending on geographical area. Age and anemia at admission were associated with co-infection status. Further longitudinal studies are needed to determine if co-infection with malaria has an impact on the severity of VL.

Dataset Information

Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania.

Publications

Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania.

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