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An assessment of the portability of ancestry informative markers between human populations.

Myles S, Stoneking M, Timpson N - BMC Med Genomics (2009)

Bottom Line: The present study assesses this assumption and evaluates the portability between worldwide populations of 10 SNPs found to be highly-differentiated within Britain (BritAIMs).Overall the median Fst across all BritAIMs is not unusually high compared to the empirical distribution.Moreover, our analyses suggest that the portability of AIMs across geographical scales (e.g. between Europe and Britain) can be limited and should therefore be taken into consideration in the design and interpretation of genetic association studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genomic Diversity, Cornell University, 175 Biotechnology Building, Ithaca, NY 14853-2703, USA. smm367@cornell.edu

ABSTRACT

Background: Recent work has shown that population stratification can have confounding effects on genetic association studies and statistical methods have been developed to correct for these effects. Subsets of markers that are highly-differentiated between populations, ancestry-informative markers (AIMs), have been used to correct for population stratification. Often AIMs are discovered in one set of populations and then employed in a different set of populations. The underlying assumption in these cases is that the population under study has the same substructure as the population in which the AIMs were discovered. The present study assesses this assumption and evaluates the portability between worldwide populations of 10 SNPs found to be highly-differentiated within Britain (BritAIMs).

Methods: We genotyped 10 BritAIMs in approximately 1000 individuals from 53 populations worldwide. We assessed the degree to which these 10 BritAIMs capture population stratification in other groups of populations by use of the Fst statistic. We used Fst values from 2750 random markers typed in the same set of individuals as an empirical distribution to which the Fst values of the 10 BritAIMs were compared.

Results: Allele frequency differences between continental groups for the BritAIMs are not unusually high. This is also the case for comparisons within continental groups distantly related to Britain. However, two BritAIMs show high Fst between European populations and two BritAIMs show high Fst between populations from the Middle East. Overall the median Fst across all BritAIMs is not unusually high compared to the empirical distribution.

Conclusion: We find that BritAIMs are generally not useful to distinguish between continental groups or within continental groups distantly related to Britain. Moreover, our analyses suggest that the portability of AIMs across geographical scales (e.g. between Europe and Britain) can be limited and should therefore be taken into consideration in the design and interpretation of genetic association studies.

No MeSH data available.


Fst values of the 2750 random markers within Europe (A) and within the Middle East (B). The Fst values of the 10 BritAIMs are indicated by vertical lines. BritAIMs that lie within the top 5% of the empirical distribution are highlighted with asterisks.
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Figure 2: Fst values of the 2750 random markers within Europe (A) and within the Middle East (B). The Fst values of the 10 BritAIMs are indicated by vertical lines. BritAIMs that lie within the top 5% of the empirical distribution are highlighted with asterisks.

Mentions: We first tested whether the 10 BritAIMs were highly differentiated among the 7 continental groups of the CEPH-HGDP panel by comparing global Fst values of the BritAIMs to the empirical distribution of global Fst values from 2750 random markers. None of the 10 BritAIMs have significantly high global Fst values (Figure 1, Table 1). We assessed population differentiation on a finer geographical scale by calculating Fst within continents. The P values for each of these comparisons are presented in Table 1. Only 4 BritAIMs showed significantly high Fst values (P < 0.05) in the within-continent analyses and these are highlighted in bold in Table 1: two BritAIMs (rs7696175, rs1460133) showed significantly high Fst within Europe and two were significant within the Middle East (rs11790408, rs12797951). Figure 2 displays the positions of the BritAIMs in the empirical Fst distributions of Europe and the Middle East.


An assessment of the portability of ancestry informative markers between human populations.

Myles S, Stoneking M, Timpson N - BMC Med Genomics (2009)

Fst values of the 2750 random markers within Europe (A) and within the Middle East (B). The Fst values of the 10 BritAIMs are indicated by vertical lines. BritAIMs that lie within the top 5% of the empirical distribution are highlighted with asterisks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2719660&req=5

Figure 2: Fst values of the 2750 random markers within Europe (A) and within the Middle East (B). The Fst values of the 10 BritAIMs are indicated by vertical lines. BritAIMs that lie within the top 5% of the empirical distribution are highlighted with asterisks.
Mentions: We first tested whether the 10 BritAIMs were highly differentiated among the 7 continental groups of the CEPH-HGDP panel by comparing global Fst values of the BritAIMs to the empirical distribution of global Fst values from 2750 random markers. None of the 10 BritAIMs have significantly high global Fst values (Figure 1, Table 1). We assessed population differentiation on a finer geographical scale by calculating Fst within continents. The P values for each of these comparisons are presented in Table 1. Only 4 BritAIMs showed significantly high Fst values (P < 0.05) in the within-continent analyses and these are highlighted in bold in Table 1: two BritAIMs (rs7696175, rs1460133) showed significantly high Fst within Europe and two were significant within the Middle East (rs11790408, rs12797951). Figure 2 displays the positions of the BritAIMs in the empirical Fst distributions of Europe and the Middle East.

Bottom Line: The present study assesses this assumption and evaluates the portability between worldwide populations of 10 SNPs found to be highly-differentiated within Britain (BritAIMs).Overall the median Fst across all BritAIMs is not unusually high compared to the empirical distribution.Moreover, our analyses suggest that the portability of AIMs across geographical scales (e.g. between Europe and Britain) can be limited and should therefore be taken into consideration in the design and interpretation of genetic association studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Genomic Diversity, Cornell University, 175 Biotechnology Building, Ithaca, NY 14853-2703, USA. smm367@cornell.edu

ABSTRACT

Background: Recent work has shown that population stratification can have confounding effects on genetic association studies and statistical methods have been developed to correct for these effects. Subsets of markers that are highly-differentiated between populations, ancestry-informative markers (AIMs), have been used to correct for population stratification. Often AIMs are discovered in one set of populations and then employed in a different set of populations. The underlying assumption in these cases is that the population under study has the same substructure as the population in which the AIMs were discovered. The present study assesses this assumption and evaluates the portability between worldwide populations of 10 SNPs found to be highly-differentiated within Britain (BritAIMs).

Methods: We genotyped 10 BritAIMs in approximately 1000 individuals from 53 populations worldwide. We assessed the degree to which these 10 BritAIMs capture population stratification in other groups of populations by use of the Fst statistic. We used Fst values from 2750 random markers typed in the same set of individuals as an empirical distribution to which the Fst values of the 10 BritAIMs were compared.

Results: Allele frequency differences between continental groups for the BritAIMs are not unusually high. This is also the case for comparisons within continental groups distantly related to Britain. However, two BritAIMs show high Fst between European populations and two BritAIMs show high Fst between populations from the Middle East. Overall the median Fst across all BritAIMs is not unusually high compared to the empirical distribution.

Conclusion: We find that BritAIMs are generally not useful to distinguish between continental groups or within continental groups distantly related to Britain. Moreover, our analyses suggest that the portability of AIMs across geographical scales (e.g. between Europe and Britain) can be limited and should therefore be taken into consideration in the design and interpretation of genetic association studies.

No MeSH data available.