Lei ZhuJaishree TripathiFrances Maureen RocamoraOlivo MiottoRob van der PluijmTill S. VossSachel MokDominic P. KwiatkowskiFrançois NostenNicholas P.J. DayNicholas J. WhiteArjen M. DondorpZbynek BozdechAung Pyae PhyoElizabeth A. AshleyFrank SmithuisKhin LinKyaw Myo TunM. Abul FaizMayfong MayxayMehul DhordaNguyen Thanh Thuy-NhienPaul N. NewtonSasithon PukrittayakameeTin M. HlaingTran Tinh HienYe HtutColumbia University Medical CenterUniversity of OxfordUniversitat BaselSwiss Tropical and Public Health Institute (Swiss TPH)UCLMahidol UniversityNuffield Department of Clinical MedicineWellcome Sanger InstituteNanyang Technological UniversityMalaria Research Group and Dev Care FoundationMahosot HospitalDefence Services Medical Research Centre2019-08-232019-08-232018-12-01Nature Communications. Vol.9, No.1 (2018)204117232-s2.0-85057616910https://repository.li.mahidol.ac.th/handle/20.500.14594/44991© 2018, The Author(s). The predisposition of parasites acquiring artemisinin resistance still remains unclear beyond the mutations in Pfk13 gene and modulation of the unfolded protein response pathway. To explore the chain of casualty underlying artemisinin resistance, we reanalyze 773 P. falciparum isolates from TRACI-study integrating TWAS, GWAS, and eQTL analyses. We find the majority of P. falciparum parasites are transcriptomically converged within each geographic site with two broader physiological profiles across the Greater Mekong Subregion (GMS). We report 8720 SNP-expression linkages in the eastern GMS parasites and 4537 in the western. The minimal overlap between them suggests differential gene regulatory networks facilitating parasite adaptations to their unique host environments. Finally, we identify two genetic and physiological backgrounds associating with artemisinin resistance in the GMS, together with a farnesyltransferase protein and a thioredoxin-like protein which may act as vital intermediators linking the Pfk13 C580Y mutation to the prolonged parasite clearance time.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPhysics and AstronomyArticleSCOPUS10.1038/s41467-018-07588-x