Multilocus Association Mapping Using Variable-Length Markov Chains

• Published in: American journal of human genetics Vol. 78; no. 6; pp. 903 - 913
• Main Author: Browning, Sharon R.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.06.2006; University of Chicago Press; Cell Press; The American Society of Human Genetics
• Subjects: Biological and medical sciences; Chromosome Mapping - methods; Crohn Disease - genetics; Cystic Fibrosis - genetics; General aspects. Genetic counseling; Genetic linkage; Genetic Markers; Genetic testing; Genetics; Genomics; Genotype & phenotype; Humans; Linkage Disequilibrium; Markov analysis; Markov Chains; Medical genetics; Medical sciences; Methods; Polymorphism, Restriction Fragment Length; Sample size; Studies; Tests; Genetic mapping; Human; Cartography; Genetics; Association; Length
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/503876

I propose a new method for association-based gene mapping that makes powerful use of multilocus data, is computationally efficient, and is straightforward to apply over large genomic regions. The approach is based on the fitting of variable-length Markov chain models, which automatically adapt to the degree of linkage disequilibrium (LD) between markers to create a parsimonious model for the LD structure. Edges of the fitted graph are tested for association with trait status. This approach can be thought of as haplotype testing with sophisticated windowing that accounts for extent of LD to reduce degrees of freedom and number of tests while maximizing information. I present analyses of two published data sets that show that this approach can have better power than single-marker tests or sliding-window haplotypic tests.