Prospects for whole-genome linkage disequilibrium mapping of common disease genes
Abstract
Recently, attention has focused on the use of whole-genome linkage disequilibrium (LD) studies to map common disease genes. Such studies would employ a dense map of single nucleotide polymorphisms (SNPs) to detect association between a marker and disease. Construction of SNP maps is currently underway. An essential issue yet to be settled is the required marker density of such maps. Here, I use population simulations to estimate the extent of LD surrounding common gene variants in the general human population as well as in isolated populations. Two main conclusions emerge from these investigations. First, a useful level of LD is unlikely to extend beyond an average distance of roughly 3 kb in the general population, which implies that approximately 500,000 SNPs will be required for whole-genome studies. Second, the extent of LD is similar in isolated populations unless the founding bottleneck is very narrow or the frequency of the variant is low (<5%).
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Before the discovery of haplotype blocks, Kruglyak's simulation study showed that under assumptions approximating modern human history, little LD would be expected beyond 3 kb.
“Before their discovery, the prevailing view of LD in humans was represented by results from the simulation study of Kruglyak16, which showed that, under assumptions that were intended to approximate the history of modern humans, little LD would be expected beyond 3 kb.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [16]
A simulation study suggested that LD might typically be too short to be useful with a SNP every 5 kb (500,000 SNPs across the genome), providing very weak LD (average correlation r2 = 0.1).
“A simulation study suggested that LD might typically be too short to be useful with a SNP every 5 kb (500,000 SNPs across the genome) providing very weak LD (average correlation r2 = 0.1) (42).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [42]
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- Authors
- Kruglyak, L.
- Affiliations
- Fred Hutch Cancer Center (US)
- Corresponding author
- Kruglyak, L
- ORCID
- Kruglyak, L
- Venue
- Nature Genetics
- Published
- 1999-06
- Volume
- 22
- Issue
- 2
- Pages
- 139-144
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- DOI
- 10.1038/9642
- OpenAlex
- W2124277514
- Cited by
- 1,416
- References
- 32
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 11 · 2018: 15 · 2017: 12 · 2016: 17 · 2015: 25 · 2014: 20 · 2013: 26 · 2012: 33
- FWCI
- 84.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- linkage disequilibrium, whole genome mapping, single nucleotide polymorphisms, marker density, population simulation, founder effect, isolated populations, genetic association, human population genetics
- MeSH terms
- Chromosome Mapping, Gene Frequency, Genetic Markers, Humans, Models, Genetic, Polymorphism, Genetic, Genetic Variation, Linkage Disequilibrium, Genome, Human, Genetic Diseases, Inborn
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