Limits...
Analysis of East Asia genetic substructure using genome-wide SNP arrays.

Tian C, Kosoy R, Lee A, Ransom M, Belmont JW, Gregersen PK, Seldin MF - PLoS ONE (2008)

Bottom Line: Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease.For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations.PCA showed substructure both between different East Asian groups and within the Han Chinese population.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Rowe Program in Human Genetics, University of California Davis, Davis, California, United States of America.

ABSTRACT
Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies.

Show MeSH

Related in: MedlinePlus

Graphic representation of additional principal components (PCs 3–8) in a diverse set of subjects of East Asian Descent.Color key shows groups as defined in Fig 1. A, PC3 and PC4. B, PC5 and PC6. C, PC7 and PC8.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2587696&req=5

pone-0003862-g002: Graphic representation of additional principal components (PCs 3–8) in a diverse set of subjects of East Asian Descent.Color key shows groups as defined in Fig 1. A, PC3 and PC4. B, PC5 and PC6. C, PC7 and PC8.

Mentions: The PCA results for PC1 and PC2 are generally consistent with the relative paired Fst values with respect to the distance separation among the different population groups. For example the position of the Korean group approximately midway between the HapMap CHB and JPT groups both graphically (Figure 1) and as discussed above for paired Fst values. It is also consistent with the closer relationship between the Dai ethnic group and the Vietnamese subjects. However, the first two PCs do not show the full relationships among the population groups. For example the Lahu ethnic group appears to be closely related to the Cambodian ethnic group (Figure 1), although the paired Fst value is relatively large (Table 1). Examination of additional PCs shows the large difference between the Lahu and Cambodian ethnic groups in PCs 3, 4 and 5 (Figure 2). Using both the Kruskal-Wallis test [23], a nonparametric alternative to the ANOVA, and a split half reliability test (see Methods) substructure was present in multiple principal components (Table 2). Substantial population substructure can be observed by the nonrandom grouping of population groups that extends through PC7.


Analysis of East Asia genetic substructure using genome-wide SNP arrays.

Tian C, Kosoy R, Lee A, Ransom M, Belmont JW, Gregersen PK, Seldin MF - PLoS ONE (2008)

Graphic representation of additional principal components (PCs 3–8) in a diverse set of subjects of East Asian Descent.Color key shows groups as defined in Fig 1. A, PC3 and PC4. B, PC5 and PC6. C, PC7 and PC8.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2587696&req=5

pone-0003862-g002: Graphic representation of additional principal components (PCs 3–8) in a diverse set of subjects of East Asian Descent.Color key shows groups as defined in Fig 1. A, PC3 and PC4. B, PC5 and PC6. C, PC7 and PC8.
Mentions: The PCA results for PC1 and PC2 are generally consistent with the relative paired Fst values with respect to the distance separation among the different population groups. For example the position of the Korean group approximately midway between the HapMap CHB and JPT groups both graphically (Figure 1) and as discussed above for paired Fst values. It is also consistent with the closer relationship between the Dai ethnic group and the Vietnamese subjects. However, the first two PCs do not show the full relationships among the population groups. For example the Lahu ethnic group appears to be closely related to the Cambodian ethnic group (Figure 1), although the paired Fst value is relatively large (Table 1). Examination of additional PCs shows the large difference between the Lahu and Cambodian ethnic groups in PCs 3, 4 and 5 (Figure 2). Using both the Kruskal-Wallis test [23], a nonparametric alternative to the ANOVA, and a split half reliability test (see Methods) substructure was present in multiple principal components (Table 2). Substantial population substructure can be observed by the nonrandom grouping of population groups that extends through PC7.

Bottom Line: Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease.For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations.PCA showed substructure both between different East Asian groups and within the Han Chinese population.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Rowe Program in Human Genetics, University of California Davis, Davis, California, United States of America.

ABSTRACT
Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies.

Show MeSH
Related in: MedlinePlus