Linkage analysis without defined pedigrees

Aaron G. Day-Williams, John Blangero, Thomas D. Dyer, Kenneth Lange, Eric M. Sobel

    Research output: Contribution to journalArticle

    29 Scopus citations

    Abstract

    The need to collect accurate and complete pedigree information has been a drawback of family-based linkage and association studies. Even in case-control studies, investigators should be aware of, and condition on, familial relationships. In single nucleotide polymorphism (SNP) genome scans, relatedness can be directly inferred from the genetic data rather than determined through interviews. Various methods of estimating relatedness have previously been implemented, most notably in PLINK. We present new fast and accurate algorithms for estimating global and local kinship coefficients from dense SNP genotypes. These algorithms require only a single pass through the SNP genotype data. We also show that these estimates can be used to cluster individuals into pedigrees. With these estimates in hand, quantitative trait locus linkage analysis proceeds via traditional variance components methods without any prior relationship information. We demonstrate the success of our algorithms on simulated and real data sets. Our procedures make linkage analysis as easy as a typical genomewide association study.

    Original languageEnglish (US)
    Pages (from-to)360-370
    Number of pages11
    JournalGenetic epidemiology
    Volume35
    Issue number5
    DOIs
    StatePublished - Jul 2011

    Keywords

    • Dynamic programming
    • GWAS
    • IBD estimation
    • Kinship coefficients
    • Method of moments
    • QTL

    ASJC Scopus subject areas

    • Epidemiology
    • Genetics(clinical)

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  • Cite this

    Day-Williams, A. G., Blangero, J., Dyer, T. D., Lange, K., & Sobel, E. M. (2011). Linkage analysis without defined pedigrees. Genetic epidemiology, 35(5), 360-370. https://doi.org/10.1002/gepi.20584