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Interactions between the\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      genome and HbS have not previously been investigated in mild malaria cases or in Ghana.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a genome-wide association analysis of\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      against human \u03b2-globin genotypes in a sample of 1,368 people with mild malaria in northern Ghana.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We replicated the previously identified associations with HbS at two parasite loci (\n                      <jats:italic>Pfsa1<\/jats:italic>\n                      and\n                      <jats:italic>Pfsa3<\/jats:italic>\n                      ).\n                      <jats:italic>Pfsa2<\/jats:italic>\n                      was absent from this population. A candidate newly identified locus within the serine\/ threonine kinase\n                      <jats:italic>FIKK4.2<\/jats:italic>\n                      , which we putatively term\n                      <jats:italic>Pfsa4<\/jats:italic>\n                      , was also associated with HbS; this finding replicated in a published sample from Mali. The\n                      <jats:italic>Pfsa1-4<\/jats:italic>\n                      mutations vary widely in frequencies across Africa, are absent or very low frequency in Asia, and are highly correlated with each-other across multiple populations. We found no strong associations with haemoglobin C.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study replicates previously reported sickle-associated loci in the\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      genome and has produced new evidence of a potential association with sickle haemoglobin at a fourth parasite locus. Further research is needed to validate the tentative fourth locus. These findings add new complexity to the emerging picture of association between human and co-evolving malaria parasite genomes, suggesting new avenues for functional exploration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-026-05956-3","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:18:25Z","timestamp":1780327105000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Associations between the Plasmodium falciparum genome and sickle haemoglobin identified in mild malaria cases from Ghana"],"prefix":"10.1186","volume":"25","author":[{"given":"William L.","family":"Hamilton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie J.","family":"Forster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaw","family":"Aniweh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Asoala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Drury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk A.","family":"Rockett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon A.","family":"Awandare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic P.","family":"Kwiatkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Band","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas N.","family":"Amenga-Etego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"5956_CR1","unstructured":"World Health Organization. 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All participants or their guardians (as appropriate) were provided detailed information sheets and gave informed consent prior to enrolment. Further approval was granted by the Wellcome Sanger Institute\u2019s Research Ethics Committee for the analysis of the samples. Sample collection was conducted by LNA, who anonymised the samples prior to making them available to the Wellcome Sanger Institute. All patient-identifiable data are securely stored by LNA and only non-patient identifiable were provided to the Wellcome Sanger Institute. The study complies with all relevant ethical regulations. This research was conducted collaboratively between researchers based at the University of Ghana, the Navrongo Health Research Centre (NHRC), the Wellcome Sanger Institute, and University of Oxford. Study conceptualisation, data analysis and interpretation, and authorship of publications were shared jointly between personnel based in Ghana and the UK.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"242"}}