Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania
| Title: | Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania |
|---|---|
| Authors: | Gavin Band; Quang Si Le; Geraldine M Clarke; Katja Kivinen; Christina Hubbart; Anna E Jeffreys; Kate Rowlands; Ellen M Leffler; Muminatou Jallow; David J Conway; Fatoumatta Sisay-Joof; Giorgio Sirugo; Umberto d'Alessandro; Ousmane B Toure; Mahamadou A Thera; Salimata Konate; Sibiri Sissoko; Valentina D Mangano; Edith C Bougouma; Sodiomon B Sirima; Lucas N Amenga-Etego; Anita K Ghansah; Abraham V O Hodgson; Michael D Wilson; Anthony Enimil; Daniel Ansong; Jennifer Evans; Subulade A Ademola; Tobias O Apinjoh; Carolyne M Ndila; Alphaxard Manjurano; Chris Drakeley; Hugh Reyburn; Nguyen Hoan Phu; Nguyen Thi Ngoc Quyen; Cao Quang Thai; Tran Tinh Hien; Yik Ying Teo; Laurens Manning; Moses Laman; Pascal Michon; Harin Karunajeewa; Peter Siba; Steve Allen; Angela Allen; Melanie Bahlo; Timothy M E Davis; Victoria Simpson; Jennifer Shelton; Chris C A Spencer; George B J Busby; Angeliki Kerasidou; Eleanor Drury; Jim Stalker; Alexander Dilthey; Alexander J Mentzer; Gil McVean; Kalifa A Bojang; Ogobara Doumbo; David Modiano; Kwadwo A Koram; Tsiri Agbenyega; Olukemi K Amodu; Eric Achidi; Thomas N Williams; Kevin Marsh; Eleanor M Riley; Malcolm Molyneux; Terrie Taylor; Sarah J Dunstan; Jeremy Farrar; Ivo Mueller; Kirk A Rockett; Dominic P Kwiatkowski |
| Contributors: | Band, Gavin; Si Le, Quang; M Clarke, Geraldine; Kivinen, Katja; Hubbart, Christina; E Jeffreys, Anna; Rowlands, Kate; M Leffler, Ellen; Jallow, Muminatou; J Conway, David; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; d'Alessandro, Umberto; B Toure, Ousmane; A Thera, Mahamadou; Konate, Salimata; Sissoko, Sibiri; Mangano, Valentina; C Bougouma, Edith; B Sirima, Sodiomon; N Amenga-Etego, Luca; K Ghansah, Anita; O Hodgson, Abraham V; D Wilson, Michael; Enimil, Anthony; Ansong, Daniel; Evans, Jennifer; A Ademola, Subulade; O Apinjoh, Tobia; M Ndila, Carolyne; Manjurano, Alphaxard; Drakeley, Chri; Reyburn, Hugh; Hoan Phu, Nguyen; Thi Ngoc Quyen, Nguyen; Quang Thai, Cao; Tinh Hien, Tran; Ying Teo, Yik; Manning, Lauren; Laman, Mose; Michon, Pascal; Karunajeewa, Harin; Siba, Peter; Allen, Steve; Allen, Angela; Bahlo, Melanie; E Davis, Timothy M; Simpson, Victoria; Shelton, Jennifer; A Spencer, Chris C; J Busby, George B; Kerasidou, Angeliki; Drury, Eleanor; Stalker, Jim; Dilthey, Alexander; J Mentzer, Alexander; McVean, Gil; A Bojang, Kalifa; Doumbo, Ogobara; Modiano, David; A Koram, Kwadwo; Agbenyega, Tsiri; K Amodu, Olukemi; Achidi, Eric; N Williams, Thoma; Marsh, Kevin; M Riley, Eleanor; Molyneux, Malcolm; Taylor, Terrie; J Dunstan, Sarah; Farrar, Jeremy; Mueller, Ivo; A Rockett, Kirk; P Kwiatkowski, Dominic |
| Publication Year: | 2019 |
| Collection: | Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: | malaria genomic epidemiology; plasmodium-falciparum; genotype |
| Description: | 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 replic- able 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 sam- ples. This large dataset will provide a foundation for further research on the genetic deter- minants of malaria resistance in diverse populations. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/31844061; info:eu-repo/semantics/altIdentifier/wos/WOS:000502769900001; volume:10; issue:1; firstpage:1; lastpage:19; numberofpages:19; journal:NATURE COMMUNICATIONS; http://hdl.handle.net/11573/1411968 |
| DOI: | 10.1038/s41467-019-13480-z |
| Availability: | http://hdl.handle.net/11573/1411968; https://doi.org/10.1038/s41467-019-13480-z |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.8B91DBD8 |
| Database: | BASE |