Engelhardt, Alexander, Rieger, Anna, Tresch, Achim and Mansmann, Ulrich (2016). Efficient Maximum Likelihood Estimation for Pedigree Data with the Sum-Product Algorithm. Hum. Hered., 82 (1-2). S. 1 - 16. BASEL: KARGER. ISSN 1423-0062

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Abstract

Objective: We analyze data sets consisting of pedigrees with age at onset of colorectal cancer (CRC) as phenotype. The occurrence of familial clusters of CRC suggests the existence of a latent, inheritable risk factor. We aimed to compute the probability of a family possessing this risk factor as well as the hazard rate increase for these risk factor carriers. Due to the inheritability of this risk factor, the estimation necessitates a costly marginalization of the likelihood. Methods: We propose an improved EM algorithm by applying factor graphs and the sum-product algorithm in the E-step. This reduces the computational complexity from exponential to linear in the number of family members. Results: Our algorithm is as precise as a direct likelihood maximization in a simulation study and a real family study on CRC risk. For 250 simulated families of size 19 and 21, the runtime of our algorithm is faster by a factor of 4 and 29, respectively. On the largest family (23 members) in the real data, our algorithm is 6 times faster. Conclusion: We introduce a flexible and run-time-efficient tool for statistical inference in biomedical event data with latent variables that opens the door for advanced analyses of pedigree data. (C) 2017 S. Karger AG, Basel

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Engelhardt, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rieger, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tresch, AchimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mansmann, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-287778
DOI: 10.1159/000475465
Journal or Publication Title: Hum. Hered.
Volume: 82
Number: 1-2
Page Range: S. 1 - 16
Date: 2016
Publisher: KARGER
Place of Publication: BASEL
ISSN: 1423-0062
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HIDDEN MARKOV-MODELS; CONVERGENCE; SEGREGATIONMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28777

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