Relatives‐based Nonparametric Analysis of Linkage


Some linkage methods do not depend on prior specification of a model of inheritance for the trait of interest. Based on identity‐by‐descent allele sharing information on pairs or sets of related individuals, these methods can be used to assess linkage to both qualitative and quantitative traits.

Keywords: identity‐by‐descent sharing; affected sib‐pairs; affected relative pairs; model‐free


Amos CI (1994) Robust variance‐components approach for assessing genetic linkage in pedigrees. American Journal of Human Genetics 54: 535–543.

Amos CI, Dawson DV and Elston RC (1990) The probabilistic determination of identity‐by‐descent sharing for pairs of relatives from pedigrees. American Journal of Human Genetics 47: 842–853.

Commenges D (1994) Robust genetic linkage analysis based on a score test of homogeneity: the weighted pairwise correlation statistic. Genetic Epidemiology 10: 87–102.

Davis S, Schroeder M, Goldin LR and Weeks DE (1996) Non‐parametric simulation‐based statistics for detecting linkage in general pedigrees. American Journal of Human Genetics 58: 867–880.

Elston RC and Stewart J (1971) A general model for the genetic analysis of pedigree data. Human Heredity 21: 523–542.

Elston RC, Buxbaum S, Jacobs KB and Olson JM (2000) Haseman and Elston revisited. Genetic Epidemiology 19: 1–17.

Gauderman WJ and Siegmund KD (2001) Gene–environment interaction and affected sib pair linkage analysis. Human Heredity 52: 34–46.

Goddard KA, Witte JS, Suarez BK, Catalona WJ and Olson JM (2001) Model‐free linkage analysis with covariates confirms linkage of prostate cancer to chromosomes 1 and 4. American Journal of Human Genetics 68: 1197–1206.

Goldgar DE (1990) Multipoint analysis of human quantitative genetic variation. American Journal of Human Genetics 47: 957–967.

Green JR and Woodrow JC (1977) Sibling method for detecting HLA‐linked genes in a disease. Tissue Antigens 9: 31–35.

Greenwood CM and Bull SB (1999) Analysis of affected sib pairs, with covariates – with and without constraints. American Journal of Human Genetics 64: 871–875.

Haseman JK and Elston RC (1972) The investigation of linkage between a quantitative trait and a marker locus. Behavioral Genetics 2: 3–19.

Idury RM and Elston RC (1997) A faster and more general hidden Markov model algorithm for multipoint likelihood calculations. Human Heredity 47: 197–202.

Kruglyak L, Daly MJ and Lander ES (1995) Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. American Journal of Human Genetics 56: 519–527.

Kruglyak L, Daly MJ, Reeve‐Daly MP and Lander ES (1996) Parametric and nonparametric linkage analysis: a unified multipoint approach. American Journal of Human Genetics 58: 1347–1363.

Lander ES and Green P (1987) Construction of multilocus genetic linkage maps in humans. Proceedings of the National Academy of Sciences of the United States of America 84: 2363–2367.

Markianos K, Daly MJ and Kruglyak L (2001) Efficient multipoint linkage analysis through reduction of inheritance space. American Journal of Human Genetics 68: 963–977.

O'Connell RJ (2001) Rapid multipoint linkage analysis via inheritance vectors in the Elston–Stewart algorithm. Human Heredity 51: 226–240.

Olson JM and Wijsman EM (1993) Linkage between quantitative trait and marker loci: methods using all relative pairs. Genetic Epidemiology 10: 87–102.

Risch N (1990) Linkage strategies for genetically complex traits. II. The power of affected relative pairs. American Journal of Human Genetics 57: 439–454.

Schaid DJ, Elston RC, Wilson AF and Tran L (1994) SAGE: Statistical Analysis for Genetic Epidemiology, Release 2.2. Computer program available from Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.

Sobel E and Lange K (1996) Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker‐sharing statistics. American Journal of Human Genetics 58: 1323–1337.

Whittemore AS and Halpern J (1994) Probability of gene identity by descent: computation and applications. Biometrics 50: 109–117.

Whittemore AS and Tu IP (1998) Simple, robust linkage tests for affected sibs. American Journal of Human Genetics 62: 1228–1242.

Further Reading

Elston RC and Cordell HJ (1999) Overview of model‐free methods for linkage analysis. In: Rao DC and Province MA (eds.) Genetic Dissection of Complex Traits, pp. 135–147. San Diego, CA: Academic Press

Goldgar DE (1998) Sib pair analysis. In: Haines JL and Pericak‐Vance MA (eds.) Gene‐mapping in Complex Human Diseases, pp. 273–303. New York: Wiley‐Liss.

Lander ES and Schork NJ (1994) Genetic dissection of complex traits. Science 265: 2037–2048.

Olson JM (1998) Linkage analysis, model‐free. In: Armitage P and Colton T (eds.) The Encyclopedia of Biostatistics, pp. 2291–2301. Chichester, UK: John Wiley.

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Gray‐McGuire, Courtney, and Olson, Jane M(Jan 2006) Relatives‐based Nonparametric Analysis of Linkage. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005402]