American Association for Cancer Research
10559965epi120703-sup-fig3.pdf (302.6 kB)

Supplementary Figure 3 from A Variable Age of Onset Segregation Model for Linkage Analysis, with Correction for Ascertainment, Applied to Glioma

Download (302.6 kB)
journal contribution
posted on 2023-03-31, 13:26 authored by Xiangqing Sun, Jaime Vengoechea, Robert Elston, Yanwen Chen, Christopher I. Amos, Georgina Armstrong, Jonine L. Bernstein, Elizabeth Claus, Faith Davis, Richard S. Houlston, Dora Il'yasova, Robert B. Jenkins, Christoffer Johansen, Rose Lai, Ching C. Lau, Yanhong Liu, Bridget J. McCarthy, Sara H. Olson, Siegal Sadetzki, Joellen Schildkraut, Sanjay Shete, Robert Yu, Nicholas A. Vick, Ryan Merrell, Margaret Wrensch, Ping Yang, Beatrice Melin, Melissa L. Bondy, Jill S. Barnholtz-Sloan

PDF file, 302K, Scatter plot of the visits at possible linked QTL locations on chromosome 17 vs. iteration.



Background: We propose a 2-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.Methods: First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N = 281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N = 74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are reestimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis.Results: Using the best-fitting segregation models in model-based multipoint linkage analysis, we identified 2 separate peaks on chromosome 17; the first agreed with a region identified by Shete and colleagues who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD).Conclusions: Our approach was able to narrow the linkage peak previously published for glioma.Impact: We provide a practical solution to model-based linkage analysis for disease affection status with variable age of onset for the kinds of pedigree data often collected for linkage analysis. Cancer Epidemiol Biomarkers Prev; 21(12); 2242–51. ©2012 AACR.

Usage metrics

    Cancer Epidemiology, Biomarkers & Prevention



    Ref. manager