Linkage and Association Studies

Ingrid B Borecki, Washington University School of Medicine, St Louis, Missouri, USA

Published online: July 2006

DOI: 10.1038/npg.els.0005483

Identification of genetic factors underlying predisposition to complex human diseases has relied on linkage studies to map the relevant loci and on association studies to evaluate the putative role of specific genetic variants on the risk for disease or on levels of quantitative risk factors. While both approaches seek an association between a genetic sequence and a phenotype of interest, their respective utility and power depend on the specific problem.

Keywords: lod scores; nonparametric linkage; case–control studies; transmission disequilibrium test; genome scans; candidate genes

Figure 1. Measured factors are in boxes, unmeasured factors are in circles. The correlation to be tested in each case is shown with the dotted line. D: disease; G: gene; M: marker.
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 References
    book Borecki IB and Suarez BK (2001) "Linkage and association: basic concepts". In: Rao DC and Province MA (eds.) Genetic Dissection of Complex Traits, pp. 45–66. San Diego, CA: Academic Press.
    book Elston RC and Cordell HJ (2001) "Overview of model-free methods for linkage analysis". In: Rao DC and Province MA (eds.) Genetic Dissection of Complex Traits, pp. 135–150. San Diego, CA: Academic Press.
    book Goldgar DE (2001) "Major strengths and weaknesses of model-free methods". In: Rao DC and Province MA (eds.) Genetic Dissection of Complex Traits, pp. 241–251. San Diego, CA: Academic Press.
    Horikawa Y, Oda N, Cox NJ, et al. (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus [see comments]. Nature Genetics 26(2): 163–175; erratum Nature Genetics 26(4): 502.
    Hugot JP, Chamaillard M, Zouali H, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease [see comments]. Nature 411(6837): 599–603.
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    book Ott J (2001) "Major strengths and weaknesses of the Lod score method". In: Rao DC and Province MA (eds.) Genetic Dissection of Complex Traits, pp. 125–132. San Diego, CA: Academic Press.
    book Rice JP, Saccone NL and Corbett J (2001) "The Lod score method". In: Rao DC and Province MA (eds.) Genetic Dissection of Complex Traits, pp. 99–114. San Diego, CA: Academic Press.
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    Van Eerdewegh P, Little RD, Dupuis J, et al. (2002) Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 418: 426–430.
 Further Reading
    Altmueller J, Palmer LJ, Fischer G, Scherb H and Wijst M (2001) Genomewide scans of complex human diseases: true linkage is hard to find. American Journal of Human Genetics 69: 936–950.
    Hirschhorn JN, Lohmueller K, Byrne E and Hirschhorn K (2002) A comprehensive review of genetic association studies. Genetics in Medicine 4: 45–61.
    Nordberg M and Tavare S (2002) Linkage equilibrium: what history has to tell us. Trends in Genetics 18: 83–90.
    book Ott J (1999) Analysis of Human Genetic Linkage, 3rd edn. Baltimore, MD: Johns Hopkins University Press.
    book Rao DC and Province MA (eds.) (2001) Genetic Dissection of Complex Traits. San Diego, CA: Academic Press.
    Tabor HK, Risch NJ and Myers RM (2002) Candidate-gene approaches for studying complex genetic traits: practical considerations. Nature Reviews Genetics 3: 391–397.

Related Sub-Topics:

Linkage Analysis | Statistical Methodology in Genetics | Gene Mapping by Disease Association
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Article Title: Linkage and Association Studies
 
How to Cite close
Borecki, Ingrid B(Jul 2006) Linkage and Association Studies. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005483]