{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T18:15:33Z","timestamp":1715537733464},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,6]],"date-time":"2005-06-06T00:00:00Z","timestamp":1118016000000},"content-version":"vor","delay-in-days":3809,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[1995,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false\u2010positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi\u2010squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false\u2010positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false\u2010positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gepi.1370120205","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T22:01:33Z","timestamp":1118527293000},"page":"163-176","source":"Crossref","is-referenced-by-count":21,"title":["Guess LOD approach: Sufficient conditions for robustness"],"prefix":"10.1002","volume":"12","author":[{"given":"John A.","family":"Williamson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher I.","family":"Amos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,6]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"213","article-title":"Robustness of the maximum\u2010likelihood (LOD) method for detecting genetic linkage","volume":"52","author":"Amos CI","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531059"},{"key":"e_1_2_1_4_1","first-page":"662","article-title":"Estimation of allele frequencies for VNTR loci","volume":"48","author":"Devlin B","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_5_1","first-page":"203","volume-title":"Genetic Analysis of Common Diseases: Applications to Predictive Factors in Coronary Disease","author":"Feldman MW","year":"1979"},{"key":"e_1_2_1_6_1","first-page":"374","article-title":"The performance of the likelihood ratio test when the model is incorrect","volume":"43","author":"Foutz RV","year":"1977","journal-title":"Ann Statistics"},{"key":"e_1_2_1_7_1","first-page":"1102","article-title":"Incorrect specification of marker allele frequencies: effects on linkage analysis","volume":"52","author":"Freimer NB","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1370070106"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320340406"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1370110403"},{"key":"e_1_2_1_11_1","first-page":"221","volume-title":"The Behavior of Maximum Likelihood Estimates under Nonstandard Conditions","author":"Huber PJ","year":"1967"},{"key":"e_1_2_1_12_1","first-page":"354","article-title":"Distribution of LOD scores under uncertain mode of inheritance","volume":"52","author":"MacLean CJ","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_13_1","first-page":"283","article-title":"Strategies for characterizing highly polymorphic markers in human gene mapping","volume":"51","author":"Ott J","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0040-5809(90)90019-R"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/01621459.1987.10478472","article-title":"Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under nonstandard conditions","volume":"82","author":"Self SG","year":"1988","journal-title":"J Am Stat Assoc"},{"key":"e_1_2_1_16_1","first-page":"374","article-title":"A resolution of the ascertainment sampling problem. II. Generalizations and numerical results","volume":"43","author":"Shute N","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_17_1","first-page":"387","article-title":"A resolution of the ascertainment sampling problem. III. Pedigrees","volume":"43","author":"Shute N","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.1370070502"}],"container-title":["Genetic Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgepi.1370120205","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gepi.1370120205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T21:15:56Z","timestamp":1698268556000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gepi.1370120205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,1]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,1]]}},"alternative-id":["10.1002\/gepi.1370120205"],"URL":"https:\/\/doi.org\/10.1002\/gepi.1370120205","archive":["Portico"],"relation":{},"ISSN":["0741-0395","1098-2272"],"issn-type":[{"value":"0741-0395","type":"print"},{"value":"1098-2272","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,1]]}}}