Linkage and Association Studies: Replication

M Daniele Fallin, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Ann E Pulver, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

Published online: January 2006

DOI: 10.1038/npg.els.0005416

Conclusions regarding identification of disease genes are currently limited by the failure to replicate linkage and association findings across studies. Issues such as heterogeneity, limited power and inadequate marker information should be considered carefully to guide design strategies most likely to provide interpretable results across studies.

Keywords: linkage; association; replication; heterogeneity; power

Figure 1. Examples of heterogeneity. Locus heterogeneity: mutations (or alleles) in two separate genes each cause disease (see sequences a and b in panel 1, which contain disease-related mutations on separate chromosomes). Allelic heterogeneity: two different mutations (alleles) in the same gene cause disease (see sequences a versus c on c12 and b, d and e on c20 in panel 1; f versus g in panel 2). Haplotype heterogeneity: identical disease mutations (alleles) have different background haplotypes (and linkage disequilibrium structures) due to different population histories (see sequence d versus g).
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    Wang K, Vieland VJ and Huang J (1999) A Bayesian approach to replication of linkage findings. Genetic Epidemiology 17 (supplement 1): S749–S754.
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 Web Links
    ePath Dopamine receptor D2 (DRD2); Locus ID: 1813.LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1813
    ePath Dopamine receptor D2 (DRD2); MIM number: 126450.OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?126450

Related Sub-Topics:

Techniques and Tools in Clinical Genetics | Linkage Analysis | Statistical Methodology in Genetics | Gene Mapping by Disease Association | Techniques and Tools in Molecular Biology
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Article Title: Linkage and Association Studies: Replication
 
How to Cite close
Fallin, M Daniele, and Pulver, Ann E(Jan 2006) Linkage and Association Studies: Replication. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005416]