التفاصيل البيبلوغرافية
| العنوان: |
Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania. |
| المؤلفون: |
Malaria Genomic Epidemiology Network, Band, Gavin, Le, Quang Si, Clarke, Geraldine M., Kivinen, Katja, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Leffler, Ellen M., Jallow, Muminatou, Conway, David J., Sisay-Joof, Fatoumatta, Sirugo, Giorgio, d'Alessandro, Umberto, Toure, Ousmane B., Thera, Mahamadou A., Konate, Salimata, Sissoko, Sibiri, Mangano, Valentina D., Bougouma, Edith C. |
| المصدر: |
Nature Communications; 12/16/2019, Vol. 10 Issue 1, p1-19, 19p |
| مصطلحات موضوعية: |
MALARIA, DISEASE susceptibility, COMMUNICABLE diseases, BIRTH control, CHROMOSOMES |
| مستخلص: |
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. Four genome-wide associated loci are currently known for malaria susceptibility. Here, the authors expand on earlier work by combining data from 11 malaria-endemic countries and additional population sequencing informing an African-enriched imputation reference panel, with findings including a previously unreported association on chromosome 6. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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