{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:44:51Z","timestamp":1790246691270,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:00:00Z","timestamp":1557705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006537","name":"Campus France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT091310"],"award-info":[{"award-number":["WT091310"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic association studies have provided new insights into the genetic variability of human complex traits with a focus mainly on continuous or binary traits. Methods have been proposed to take into account disease heterogeneity between subgroups of patients when studying common variants but none was specifically designed for rare variants. Because rare variants are expected to have stronger effects and to be more heterogeneously distributed among cases than common ones, subgroup analyses might be particularly attractive in this context. To address this issue, we propose an extension of burden tests by using a multinomial regression model, which enables association tests between rare variants and multicategory phenotypes. We evaluated the type I error and the power of two burden tests, CAST and WSS, by simulating data under different scenarios. In the case of genetic heterogeneity between case subgroups, we showed an advantage of multinomial regression over logistic regression, which considers all the cases against the controls. We replicated these results on real data from Moyamoya disease where the burden tests performed better when cases were stratified according to age\u2010of\u2010onset. We implemented the functions for association tests in the R package \u201cRavages\u201d available on Github.<\/jats:p>","DOI":"10.1002\/gepi.22210","type":"journal-article","created":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T04:03:57Z","timestamp":1557806637000},"page":"646-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Rare variant association testing for multicategory phenotype"],"prefix":"10.1002","volume":"43","author":[{"given":"Ozvan","family":"Bocher","sequence":"first","affiliation":[{"name":"Univ Brest Inserm, EFS, UMR 1078, GGB  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-7170","authenticated-orcid":false,"given":"Ga\u00eblle","family":"Marenne","sequence":"additional","affiliation":[{"name":"Univ Brest Inserm, EFS, UMR 1078, GGB  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Saint Pierre","sequence":"additional","affiliation":[{"name":"Univ Brest Inserm, EFS, UMR 1078, GGB  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Univ Brest Inserm, EFS, UMR 1078, GGB  Brest France"},{"name":"CHU Brest  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Guey","sequence":"additional","affiliation":[{"name":"Inserm UMR\u2010S1161, G\u00e9n\u00e9tique et Physiopathologie des Maladies C\u00e9r\u00e9bro\u2010vasculaires Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Tournier\u2010Lasserve","sequence":"additional","affiliation":[{"name":"Inserm UMR\u2010S1161, G\u00e9n\u00e9tique et Physiopathologie des Maladies C\u00e9r\u00e9bro\u2010vasculaires Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Perdry","sequence":"additional","affiliation":[{"name":"CESP Inserm, U1018, UFR M\u00e9decine Univ Paris\u2010Sud, Universit\u00e9 Paris\u2010Saclay  Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"G\u00e9nin","sequence":"additional","affiliation":[{"name":"Univ Brest Inserm, EFS, UMR 1078, GGB  Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"e_1_2_8_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-012-1191-1"},{"key":"e_1_2_8_1_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-102209-163421"},{"key":"e_1_2_8_1_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000954"},{"key":"e_1_2_8_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.f.136"},{"issue":"2","key":"e_1_2_8_1_6_1","first-page":"203","article-title":"JBASE: Joint Bayesian analysis of subphenotypes and epistasis","volume":"32","author":"Colak R.","year":"2016","journal-title":"Bioinformatics (Oxford, England)"},{"key":"e_1_2_8_1_7_1","article-title":"Package \u201cmlogit\u201d","author":"Croissant Y.","year":"2015","journal-title":"CRAN"},{"key":"e_1_2_8_1_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-019-2611-1"},{"key":"e_1_2_8_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2554"},{"key":"e_1_2_8_1_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.92"},{"key":"e_1_2_8_1_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000288704"},{"key":"e_1_2_8_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw075"},{"key":"e_1_2_8_1_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq352"},{"key":"e_1_2_8_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.007"},{"key":"e_1_2_8_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.06.024"},{"key":"e_1_2_8_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3751"},{"key":"e_1_2_8_1_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000384"},{"key":"e_1_2_8_1_18_1","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2012.89"},{"key":"e_1_2_8_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2006.09.003"},{"key":"e_1_2_8_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20486"},{"key":"e_1_2_8_1_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001322"},{"key":"e_1_2_8_1_22_1","unstructured":"Perdry H. &Bocher O.(2018).Package \u2018Ravages\u2019: Rare Variant Analysis and Genetic Simulations. 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