{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:15:23Z","timestamp":1792602923257,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>We propose two novel one\u2010sample Mendelian randomization (MR) approaches to causal inference from count\u2010type health outcomes, tailored to both equidispersion and overdispersion conditions. Selecting valid single\u2010nucleotide polymorphisms (SNPs) as instrumental variables (IVs) poses a key challenge for MR approaches, as it requires meeting the necessary IV assumptions. To bolster the proposed approaches by addressing violations of IV assumptions, we incorporate a process for removing invalid SNPs that violate the assumptions. In simulations, our proposed approaches demonstrate robustness to the violations, delivering valid estimates, and interpretable type\u2010I errors and statistical power. This increases the practical applicability of the models. We applied the proposed approaches to evaluate the causal effect of fetal hemoglobin (HbF) on the vaso\u2010occlusive crisis and acute chest syndrome (ACS) events in patients with sickle cell disease (SCD) and revealed the causal relation between HbF and ACS events in these patients. We also developed a user\u2010friendly Shiny web application to facilitate researchers' exploration of causal relations.<\/jats:p>","DOI":"10.1002\/gepi.22602","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T07:19:57Z","timestamp":1730791197000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel One\u2010Sample Mendelian Randomization Approach for Count\u2010Type Outcomes That Is Robust to Correlated and Uncorrelated Pleiotropic Effects"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9882-0362","authenticated-orcid":false,"given":"Janaka S. S.","family":"Liyanage","sequence":"first","affiliation":[{"name":"Biostatistics Core, Department of Oncology, Karmanos Cancer Institute, School of Medicine Wayne State University Detroit Michigan USA"},{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane S.","family":"Hankins","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"},{"name":"Departments of Global Pediatric Medicine and Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremie H.","family":"Estepp","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"},{"name":"Departments of Global Pediatric Medicine and Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deokumar","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5542-6891","authenticated-orcid":false,"given":"Sara R.","family":"Rashkin","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"},{"name":"Department of Genetics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"},{"name":"Department of Computer Science The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Statistics and Probability Michigan State University East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomi","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Hematology St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolian","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15555.3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280215597579"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4498"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt093"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-02-769661"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/00223890802634175"},{"key":"e_1_2_9_9_1","unstructured":"Fox J. Z.Nie andJ.Byrnes.2022.sem: Structural Equation Models. R Package Version 3.1\u201015.https:\/\/CRAN.R-project.org\/web\/packages\/sem\/index.html."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a114001"},{"key":"e_1_2_9_11_1","unstructured":"Ghalanos A. andS.Theussl.2015.Rsolnp: General Non\u2010Linear Optimization Using Augmented Lagrange Multiplier Method. R Package Version 1.16."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1037\/adb0000669"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27228"},{"key":"e_1_2_9_14_1","unstructured":"Hartig F.2022.DHARMa: Residual Diagnostics for Hierarchical (Multi\u2010Level\/Mixed) Regression Models. R Package Version 0.4.6.https:\/\/CRAN.R-project.org\/web\/packages\/DHARMa\/."},{"key":"e_1_2_9_15_1","volume-title":"Principles of Econometrics","author":"Hill R. C.","year":"2011"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-3242-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/589110"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004634"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23457"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23232"},{"key":"e_1_2_9_21_1","volume-title":"Generalized Linear Mixed Models: Modern Concepts, Methods and Applications","author":"Stroup W. W.","year":"2012"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ece3.3807"},{"issue":"10091","key":"e_1_2_9_23_1","first-page":"311","article-title":"Detection of Widespread Horizontal Pleiotropy in Causal Relationships Inferred From Mendelian Randomization Between Complex Traits and Diseases. Nature Ware, R. E., de Montalembert, M., Tshilolo, L. & Abboud, M. R. (2017). Sickle Cell Disease","volume":"390","author":"Verbanck M.","year":"2018","journal-title":"Lancet"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804799105"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15011"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.05.014"},{"key":"e_1_2_9_27_1","unstructured":"Ye Y.1987. \u201cInterior Algorithms for Linear Quadratic and Linearly Constrained Non\u2010Linear Programming.\u201d Ph.D. Thesis Department of Engineering\u2010Economic Systems Stanford University."}],"container-title":["Genetic Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gepi.22602","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gepi.22602","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gepi.22602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:12:33Z","timestamp":1772982753000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gepi.22602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,5]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/gepi.22602"],"URL":"https:\/\/doi.org\/10.1002\/gepi.22602","archive":["Portico"],"relation":{},"ISSN":["0741-0395","1098-2272"],"issn-type":[{"value":"0741-0395","type":"print"},{"value":"1098-2272","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,5]]},"assertion":[{"value":"2024-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22602"}}