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• W2091853774 abstract "SummaryWhen affected probands and their biological parents are genotyped at a candidate gene or a marker, the resulting case-parents–triad data enable powerful tests for linkage in the presence of association. When linkage disequilibrium has been detected in such a study, the investigator may wish to look further for possible parent-of-origin effects. If, for example, the transmission/disequilibrium test restricted to fathers is statistically significant, whereas that restricted to mothers is not, the investigator might interpret this as evidence for nonexpression of the maternally derived disease gene—that is, imprinting. This report reviews existing methods for detection of parent-of-origin effects, showing that each can be invalid under certain scenarios. Two new methods are proposed, based on application of likelihood-based inference after stratification on both the parental mating type and the inherited number of copies of the allele under study. If there are no maternal genetic effects expressed prenatally during gestation, the parental-asymmetry test is powerful and provides valid estimation of a parent-of-origin parameter. For diseases for which there could be maternal effects on risk, the parent-of-origin likelihood-ratio test provides a robust alternative. Simulations based on an admixed population demonstrate good operating characteristics for these procedures, under diverse scenarios. When affected probands and their biological parents are genotyped at a candidate gene or a marker, the resulting case-parents–triad data enable powerful tests for linkage in the presence of association. When linkage disequilibrium has been detected in such a study, the investigator may wish to look further for possible parent-of-origin effects. If, for example, the transmission/disequilibrium test restricted to fathers is statistically significant, whereas that restricted to mothers is not, the investigator might interpret this as evidence for nonexpression of the maternally derived disease gene—that is, imprinting. This report reviews existing methods for detection of parent-of-origin effects, showing that each can be invalid under certain scenarios. Two new methods are proposed, based on application of likelihood-based inference after stratification on both the parental mating type and the inherited number of copies of the allele under study. If there are no maternal genetic effects expressed prenatally during gestation, the parental-asymmetry test is powerful and provides valid estimation of a parent-of-origin parameter. For diseases for which there could be maternal effects on risk, the parent-of-origin likelihood-ratio test provides a robust alternative. Simulations based on an admixed population demonstrate good operating characteristics for these procedures, under diverse scenarios." @default.
• W2091853774 created "2016-06-24" @default.
• W2091853774 creator A5078074754 @default.
• W2091853774 date "1999-07-01" @default.
• W2091853774 modified "2023-10-03" @default.
• W2091853774 title "Methods for Detection of Parent-of-Origin Effects in Genetic Studies of Case-Parents Triads" @default.
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• W2091853774 doi "https://doi.org/10.1086/302466" @default.
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