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Dysregulation of complement activation is among emerging candidates responsible for disease pathogenesis. In a targeted exomic sequencing study of 609 women with preeclampsia and 2092 non-preeclamptic controls, we identified 14 variants within nine genes coding for components of the membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense variants in the\n                    <jats:italic>C5<\/jats:italic>\n                    gene that predispose to preeclampsia (rs200674959: I1296V, OR (CI95)\u2009=\u200924.13 (1.25\u2013467.43),\n                    <jats:italic>p<\/jats:italic>\n                    value\u2009=\u20090.01 and rs147430470: I330T, OR (CI95)\u2009=\u200922.75 (1.17\u2013440.78),\n                    <jats:italic>p<\/jats:italic>\n                    value\u2009=\u20090.01). In addition, one predisposing rare variant and one protective rare variant were discovered in\n                    <jats:italic>C6<\/jats:italic>\n                    (rs41271067: D396G, OR (CI95)\u2009=\u20092.93 (1.18\u20137.10),\n                    <jats:italic>p<\/jats:italic>\n                    value\u2009=\u20090.01 and rs114609505: T190I, 0.02 OR (CI95)\u2009=\u20090.47 (0.22\u20130.92),\n                    <jats:italic>p<\/jats:italic>\n                    value\u2009=\u20090.02). The results suggest that variants in the terminal complement pathway predispose to preeclampsia.\n                  <\/jats:p>","DOI":"10.1038\/s41435-024-00310-6","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T11:53:52Z","timestamp":1734436432000},"page":"22-26","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Understanding rare genetic variants within the terminal pathway of complement system in preeclampsia"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4397-8415","authenticated-orcid":false,"given":"A. 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She has been a principal investigator for Apellis Pharmaceuticals and Novartis International AG. She also received royalty from UptoDate. HL received honoraria from Orion Corporation. JPA is part of the Scientific Advisory Board of Complement Corporation and Kypha, Inc., Scientific Advisory Board. Furthermore, he served as a consultant in Celldex Therapeutics, formerly Avant Immunotherapeutics, Inc., Biothera and Clinical Pharmacy Services, CDMI. SM received honoraria from Alexion, AstraZeneca Rare Disease, Biogen, Merck, Pfizer, and UCB, and research funding from Alexion.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}