TY - JOUR
T1 - Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania
AU - Malaria Genomic Epidemiology Network
AU - Band, Gavin
AU - Le, Quang Si
AU - Clarke, Geraldine M.
AU - Kivinen, Katja
AU - Hubbart, Christina
AU - Jeffreys, Anna E.
AU - Rowlands, Kate
AU - Leffler, Ellen M.
AU - Jallow, Muminatou
AU - Conway, David J.
AU - Sisay-Joof, Fatoumatta
AU - Sirugo, Giorgio
AU - d’Alessandro, Umberto
AU - Toure, Ousmane B.
AU - Thera, Mahamadou A.
AU - Konate, Salimata
AU - Sissoko, Sibiri
AU - Mangano, Valentina D.
AU - Bougouma, Edith C.
AU - Sirima, Sodiomon B.
AU - Amenga-Etego, Lucas N.
AU - Ghansah, Anita K.
AU - Hodgson, Abraham V.O.
AU - Wilson, Michael D.
AU - Enimil, Anthony
AU - Ansong, Daniel
AU - Evans, Jennifer
AU - Ademola, Subulade A.
AU - Apinjoh, Tobias O.
AU - Ndila, Carolyne M.
AU - Manjurano, Alphaxard
AU - Drakeley, Chris
AU - Reyburn, Hugh
AU - Phu, Nguyen Hoan
AU - Quyen, Nguyen Thi Ngoc
AU - Thai, Cao Quang
AU - Hien, Tran Tinh
AU - Teo, Yik Ying
AU - Manning, Laurens
AU - Laman, Moses
AU - Michon, Pascal
AU - Karunajeewa, Harin
AU - Siba, Peter
AU - Allen, Steve
AU - Allen, Angela
AU - Bahlo, Melanie
AU - Davis, Timothy M.E.
AU - Simpson, Victoria
AU - Shelton, Jennifer
AU - Spencer, Chris C.A.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076625069&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13480-z
DO - 10.1038/s41467-019-13480-z
M3 - Article
C2 - 31844061
AN - SCOPUS:85076625069
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5732
ER -
