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Worldwide population differentiation at disease-associated SNPs
BACKGROUND: Recent genome-wide association (GWA) studies have provided compelling evidence of association between genetic variants and common complex diseases. These studies have made use of cases and controls almost exclusively from populations of European ancestry and little is known about the fre...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440747/ https://www.ncbi.nlm.nih.gov/pubmed/18533027 http://dx.doi.org/10.1186/1755-8794-1-22 |
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author | Myles, Sean Davison, Dan Barrett, Jeffrey Stoneking, Mark Timpson, Nic |
author_facet | Myles, Sean Davison, Dan Barrett, Jeffrey Stoneking, Mark Timpson, Nic |
author_sort | Myles, Sean |
collection | PubMed |
description | BACKGROUND: Recent genome-wide association (GWA) studies have provided compelling evidence of association between genetic variants and common complex diseases. These studies have made use of cases and controls almost exclusively from populations of European ancestry and little is known about the frequency of risk alleles in other populations. The present study addresses the transferability of disease associations across human populations by examining levels of population differentiation at disease-associated single nucleotide polymorphisms (SNPs). METHODS: We genotyped ~1000 individuals from 53 populations worldwide at 25 SNPs which show robust association with 6 complex human diseases (Crohn's disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, coronary artery disease and obesity). Allele frequency differences between populations for these SNPs were measured using Fst. The Fst values for the disease-associated SNPs were compared to Fst values from 2750 random SNPs typed in the same set of individuals. RESULTS: On average, disease SNPs are not significantly more differentiated between populations than random SNPs in the genome. Risk allele frequencies, however, do show substantial variation across human populations and may contribute to differences in disease prevalence between populations. We demonstrate that, in some cases, risk allele frequency differences are unusually high compared to random SNPs and may be due to the action of local (i.e. geographically-restricted) positive natural selection. Moreover, some risk alleles were absent or fixed in a population, which implies that risk alleles identified in one population do not necessarily account for disease prevalence in all human populations. CONCLUSION: Although differences in risk allele frequencies between human populations are not unusually large and are thus likely not due to positive local selection, there is substantial variation in risk allele frequencies between populations which may account for differences in disease prevalence between human populations. |
format | Text |
id | pubmed-2440747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-24407472008-06-27 Worldwide population differentiation at disease-associated SNPs Myles, Sean Davison, Dan Barrett, Jeffrey Stoneking, Mark Timpson, Nic BMC Med Genomics Research Article BACKGROUND: Recent genome-wide association (GWA) studies have provided compelling evidence of association between genetic variants and common complex diseases. These studies have made use of cases and controls almost exclusively from populations of European ancestry and little is known about the frequency of risk alleles in other populations. The present study addresses the transferability of disease associations across human populations by examining levels of population differentiation at disease-associated single nucleotide polymorphisms (SNPs). METHODS: We genotyped ~1000 individuals from 53 populations worldwide at 25 SNPs which show robust association with 6 complex human diseases (Crohn's disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, coronary artery disease and obesity). Allele frequency differences between populations for these SNPs were measured using Fst. The Fst values for the disease-associated SNPs were compared to Fst values from 2750 random SNPs typed in the same set of individuals. RESULTS: On average, disease SNPs are not significantly more differentiated between populations than random SNPs in the genome. Risk allele frequencies, however, do show substantial variation across human populations and may contribute to differences in disease prevalence between populations. We demonstrate that, in some cases, risk allele frequency differences are unusually high compared to random SNPs and may be due to the action of local (i.e. geographically-restricted) positive natural selection. Moreover, some risk alleles were absent or fixed in a population, which implies that risk alleles identified in one population do not necessarily account for disease prevalence in all human populations. CONCLUSION: Although differences in risk allele frequencies between human populations are not unusually large and are thus likely not due to positive local selection, there is substantial variation in risk allele frequencies between populations which may account for differences in disease prevalence between human populations. BioMed Central 2008-06-04 /pmc/articles/PMC2440747/ /pubmed/18533027 http://dx.doi.org/10.1186/1755-8794-1-22 Text en Copyright © 2008 Myles et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Myles, Sean Davison, Dan Barrett, Jeffrey Stoneking, Mark Timpson, Nic Worldwide population differentiation at disease-associated SNPs |
title | Worldwide population differentiation at disease-associated SNPs |
title_full | Worldwide population differentiation at disease-associated SNPs |
title_fullStr | Worldwide population differentiation at disease-associated SNPs |
title_full_unstemmed | Worldwide population differentiation at disease-associated SNPs |
title_short | Worldwide population differentiation at disease-associated SNPs |
title_sort | worldwide population differentiation at disease-associated snps |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440747/ https://www.ncbi.nlm.nih.gov/pubmed/18533027 http://dx.doi.org/10.1186/1755-8794-1-22 |
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