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Analysis and application of European genetic substructure using 300 K SNP information.

Tian C, Plenge RM, Ransom M, Lee A, Villoslada P, Selmi C, Klareskog L, Pulver AE, Qi L, Gregersen PK, Seldin MF - PLoS Genet. (2008)

Bottom Line: A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations.In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information.The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

View Article: PubMed Central - PubMed

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

ABSTRACT
European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

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European Substructure Analysis of a Diverse Set of Individuals of European Descent(A) Graphic representation of the first two PCs for 952 individuals genotyped with 300K SNPs.(B) Color code shows subgroup of individuals with more detailed grandparental origin information. Each color-coded individual had 4GP of origin information with the exception of the AJA group. The individuals included 14 Spanish (SPN), 28 Italian (ITN), eight Greek (GRK), 11 German (GERM), 52 IRISH, five United Kingdom (UK), three Scandinavian (SCAN), and two Netherland (NETH). For the Ashkenazi Jewish individuals, 38 had 4GP information (AJA_4GP), and 220 participants were self identified as Ashkenazi Jewish (AJA) but without other information.(C) The STRUCTURE analyses shows results from the same participant set using three random sets of >3,500 SNPs for assessment of the number of population groups (K). The ordinate shows the Ln probability (mean +/− SD) corresponding to the number of clusters.(D) STRUCTURE results under the assumption of two population groups (K = 2). The proportion of each cluster group (population) for each individual is shown by the color code.
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pgen-0040004-g001: European Substructure Analysis of a Diverse Set of Individuals of European Descent(A) Graphic representation of the first two PCs for 952 individuals genotyped with 300K SNPs.(B) Color code shows subgroup of individuals with more detailed grandparental origin information. Each color-coded individual had 4GP of origin information with the exception of the AJA group. The individuals included 14 Spanish (SPN), 28 Italian (ITN), eight Greek (GRK), 11 German (GERM), 52 IRISH, five United Kingdom (UK), three Scandinavian (SCAN), and two Netherland (NETH). For the Ashkenazi Jewish individuals, 38 had 4GP information (AJA_4GP), and 220 participants were self identified as Ashkenazi Jewish (AJA) but without other information.(C) The STRUCTURE analyses shows results from the same participant set using three random sets of >3,500 SNPs for assessment of the number of population groups (K). The ordinate shows the Ln probability (mean +/− SD) corresponding to the number of clusters.(D) STRUCTURE results under the assumption of two population groups (K = 2). The proportion of each cluster group (population) for each individual is shown by the color code.

Mentions: The clustering of individuals for PC1 and PC2 corresponded to self-reported regional and ethnic origins (Figure 1A and 1B). This is best illustrated when considering only those participants with the same grandparental country of origin and those individuals that indicated Ashkenazi Jewish ancestry (Figure 1B). Similar to our previous studies using smaller sets of SNPs, the clustering of individuals of Ashkenazi Jewish ancestry does not correspond to grandparental European country of origin, which was diverse [6].


Analysis and application of European genetic substructure using 300 K SNP information.

Tian C, Plenge RM, Ransom M, Lee A, Villoslada P, Selmi C, Klareskog L, Pulver AE, Qi L, Gregersen PK, Seldin MF - PLoS Genet. (2008)

European Substructure Analysis of a Diverse Set of Individuals of European Descent(A) Graphic representation of the first two PCs for 952 individuals genotyped with 300K SNPs.(B) Color code shows subgroup of individuals with more detailed grandparental origin information. Each color-coded individual had 4GP of origin information with the exception of the AJA group. The individuals included 14 Spanish (SPN), 28 Italian (ITN), eight Greek (GRK), 11 German (GERM), 52 IRISH, five United Kingdom (UK), three Scandinavian (SCAN), and two Netherland (NETH). For the Ashkenazi Jewish individuals, 38 had 4GP information (AJA_4GP), and 220 participants were self identified as Ashkenazi Jewish (AJA) but without other information.(C) The STRUCTURE analyses shows results from the same participant set using three random sets of >3,500 SNPs for assessment of the number of population groups (K). The ordinate shows the Ln probability (mean +/− SD) corresponding to the number of clusters.(D) STRUCTURE results under the assumption of two population groups (K = 2). The proportion of each cluster group (population) for each individual is shown by the color code.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211544&req=5

pgen-0040004-g001: European Substructure Analysis of a Diverse Set of Individuals of European Descent(A) Graphic representation of the first two PCs for 952 individuals genotyped with 300K SNPs.(B) Color code shows subgroup of individuals with more detailed grandparental origin information. Each color-coded individual had 4GP of origin information with the exception of the AJA group. The individuals included 14 Spanish (SPN), 28 Italian (ITN), eight Greek (GRK), 11 German (GERM), 52 IRISH, five United Kingdom (UK), three Scandinavian (SCAN), and two Netherland (NETH). For the Ashkenazi Jewish individuals, 38 had 4GP information (AJA_4GP), and 220 participants were self identified as Ashkenazi Jewish (AJA) but without other information.(C) The STRUCTURE analyses shows results from the same participant set using three random sets of >3,500 SNPs for assessment of the number of population groups (K). The ordinate shows the Ln probability (mean +/− SD) corresponding to the number of clusters.(D) STRUCTURE results under the assumption of two population groups (K = 2). The proportion of each cluster group (population) for each individual is shown by the color code.
Mentions: The clustering of individuals for PC1 and PC2 corresponded to self-reported regional and ethnic origins (Figure 1A and 1B). This is best illustrated when considering only those participants with the same grandparental country of origin and those individuals that indicated Ashkenazi Jewish ancestry (Figure 1B). Similar to our previous studies using smaller sets of SNPs, the clustering of individuals of Ashkenazi Jewish ancestry does not correspond to grandparental European country of origin, which was diverse [6].

Bottom Line: A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations.In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information.The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

View Article: PubMed Central - PubMed

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

ABSTRACT
European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.

Show MeSH
Related in: MedlinePlus