Limits...
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.

Show MeSH

Related in: MedlinePlus

Principal Component Analysis Shows Chromosome 8 InversionThe selected informative SNPs from a 3.8 Mb segment of Chromosome 8 shows the same PC score distribution as the entire SNP set for the second PC in analysis of “northern” European individuals. The graph shows the position of each of 382 tested individuals for the second axis in the PCA using 500K SNPs (ordinate) and the position based on analysis using 20 selected SNPs from the 3.8 Mb segment of Chromosome 8 (abscissa). The 20 selected SNPs were those with the highest In between the outer groups in an independent dataset separated by a minimum of 50 kb.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211544&req=5

pgen-0040004-g005: Principal Component Analysis Shows Chromosome 8 InversionThe selected informative SNPs from a 3.8 Mb segment of Chromosome 8 shows the same PC score distribution as the entire SNP set for the second PC in analysis of “northern” European individuals. The graph shows the position of each of 382 tested individuals for the second axis in the PCA using 500K SNPs (ordinate) and the position based on analysis using 20 selected SNPs from the 3.8 Mb segment of Chromosome 8 (abscissa). The 20 selected SNPs were those with the highest In between the outer groups in an independent dataset separated by a minimum of 50 kb.

Mentions: Inspection of the second axis of the Northern European subset (see Figure 4A and 4B), also showed an unexpected grouping of individuals on the Y axis into three separate groups. When we ascertained informative SNPs between the top and bottom groups, all of the SNPs with In values >0.02 were found to be located in a 3.8 Mb segment of human Chromosome 8 (8.135 – 11.936 Mb). This region has been previously shown to contain a common inversion within European populations [24,25]. When only SNPs within this interval were used the distribution of the individuals formed the same grouping of three clusters as found using the entire 500K set (data not shown). As expected two dominant haplotypes (A and B) were ascertained with twenty selected markers with very large Ins and described the same three individual groups (AA, AB, and BB) and were highly correlated (r2 = 0.83) (Figure 5). Although the λgc in the entire NARAC case-control dataset is decreased from 1.073 to 1.048 by considering this axis, our analyses indicate that the position of individuals on this axis is almost completely due to this localized inversion. This region is presumably identified by PCA because of the long stretch of linkage disequilibrium caused by the chromosomal inversion.


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)

Principal Component Analysis Shows Chromosome 8 InversionThe selected informative SNPs from a 3.8 Mb segment of Chromosome 8 shows the same PC score distribution as the entire SNP set for the second PC in analysis of “northern” European individuals. The graph shows the position of each of 382 tested individuals for the second axis in the PCA using 500K SNPs (ordinate) and the position based on analysis using 20 selected SNPs from the 3.8 Mb segment of Chromosome 8 (abscissa). The 20 selected SNPs were those with the highest In between the outer groups in an independent dataset separated by a minimum of 50 kb.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-0040004-g005: Principal Component Analysis Shows Chromosome 8 InversionThe selected informative SNPs from a 3.8 Mb segment of Chromosome 8 shows the same PC score distribution as the entire SNP set for the second PC in analysis of “northern” European individuals. The graph shows the position of each of 382 tested individuals for the second axis in the PCA using 500K SNPs (ordinate) and the position based on analysis using 20 selected SNPs from the 3.8 Mb segment of Chromosome 8 (abscissa). The 20 selected SNPs were those with the highest In between the outer groups in an independent dataset separated by a minimum of 50 kb.
Mentions: Inspection of the second axis of the Northern European subset (see Figure 4A and 4B), also showed an unexpected grouping of individuals on the Y axis into three separate groups. When we ascertained informative SNPs between the top and bottom groups, all of the SNPs with In values >0.02 were found to be located in a 3.8 Mb segment of human Chromosome 8 (8.135 – 11.936 Mb). This region has been previously shown to contain a common inversion within European populations [24,25]. When only SNPs within this interval were used the distribution of the individuals formed the same grouping of three clusters as found using the entire 500K set (data not shown). As expected two dominant haplotypes (A and B) were ascertained with twenty selected markers with very large Ins and described the same three individual groups (AA, AB, and BB) and were highly correlated (r2 = 0.83) (Figure 5). Although the λgc in the entire NARAC case-control dataset is decreased from 1.073 to 1.048 by considering this axis, our analyses indicate that the position of individuals on this axis is almost completely due to this localized inversion. This region is presumably identified by PCA because of the long stretch of linkage disequilibrium caused by the chromosomal inversion.

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