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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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STRUCTURE Analysis Using 1,400 ESAIMs Selected for North/South InformationAnalysis was performed without any prior population assignment using STRUCTURE under the assumption of two population groups (K = 2). The results are shown for only individuals not used in selection of the north/south-ESIAMs. The individual individuals and 90% confidence limits are shown for selected groups with ethnic and grandparental origins (see Figure S1 for entire results). The individuals grouped by self identification included: Ashkenazi 4GP; Ashkenazi Jewish (without 4GP information) (AJA); Greek (GRK); Italian (ITN); Spanish (SPN); German (GERM); Scandinavian (SCAN); United Kingdom (UK); and Irish.
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pgen-0040004-g003: STRUCTURE Analysis Using 1,400 ESAIMs Selected for North/South InformationAnalysis was performed without any prior population assignment using STRUCTURE under the assumption of two population groups (K = 2). The results are shown for only individuals not used in selection of the north/south-ESIAMs. The individual individuals and 90% confidence limits are shown for selected groups with ethnic and grandparental origins (see Figure S1 for entire results). The individuals grouped by self identification included: Ashkenazi 4GP; Ashkenazi Jewish (without 4GP information) (AJA); Greek (GRK); Italian (ITN); Spanish (SPN); German (GERM); Scandinavian (SCAN); United Kingdom (UK); and Irish.

Mentions: The STRUCTURE results (K = 2) from individuals with 4 grandparental data (not used for ESAIM selection) showed separation of most of the 220 self-identified individuals of Ashkenazi Jewish heritage (mean 83% south; median, 87%) from 37 individuals of Western, Northern or Central heritage belonging to the “northern” group (mean 4% south; median, 3%), and 51 individuals of Greek, Italian, or Spanish origin were intermediate (mean 41% south; median, 42%) (Figures 3 and S1). These 1441 north/south-ESAIM showed small confidence limits in the assignments; of the total of 677 individual individuals not used in ESAIM selection the maximum 90% Bayesian confidence interval (CI) was 21.1% (e.g. 13.7 % south, 90% CI 2.6 % – 23.0 %) and the median CI was 13.9%. Smaller north/south-ESAIM sets showed strong correlations with the 1441 set e.g. 384 ESAIMs (r2 = 0.970) (Figure S2). However, the smaller north/south-ESAIM sets showed somewhat broader confidence limits (e.g. 384 north/south ESAIM set showed maximum CI = 38.9% and a median CI = 17.1%. However, these differences are unlikely to affect most studies. The larger number of north/south-ESAIMs may be useful if a very homogeneous set of individuals of a particular ethnic group is desired for a specific study.


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)

STRUCTURE Analysis Using 1,400 ESAIMs Selected for North/South InformationAnalysis was performed without any prior population assignment using STRUCTURE under the assumption of two population groups (K = 2). The results are shown for only individuals not used in selection of the north/south-ESIAMs. The individual individuals and 90% confidence limits are shown for selected groups with ethnic and grandparental origins (see Figure S1 for entire results). The individuals grouped by self identification included: Ashkenazi 4GP; Ashkenazi Jewish (without 4GP information) (AJA); Greek (GRK); Italian (ITN); Spanish (SPN); German (GERM); Scandinavian (SCAN); United Kingdom (UK); and Irish.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-0040004-g003: STRUCTURE Analysis Using 1,400 ESAIMs Selected for North/South InformationAnalysis was performed without any prior population assignment using STRUCTURE under the assumption of two population groups (K = 2). The results are shown for only individuals not used in selection of the north/south-ESIAMs. The individual individuals and 90% confidence limits are shown for selected groups with ethnic and grandparental origins (see Figure S1 for entire results). The individuals grouped by self identification included: Ashkenazi 4GP; Ashkenazi Jewish (without 4GP information) (AJA); Greek (GRK); Italian (ITN); Spanish (SPN); German (GERM); Scandinavian (SCAN); United Kingdom (UK); and Irish.
Mentions: The STRUCTURE results (K = 2) from individuals with 4 grandparental data (not used for ESAIM selection) showed separation of most of the 220 self-identified individuals of Ashkenazi Jewish heritage (mean 83% south; median, 87%) from 37 individuals of Western, Northern or Central heritage belonging to the “northern” group (mean 4% south; median, 3%), and 51 individuals of Greek, Italian, or Spanish origin were intermediate (mean 41% south; median, 42%) (Figures 3 and S1). These 1441 north/south-ESAIM showed small confidence limits in the assignments; of the total of 677 individual individuals not used in ESAIM selection the maximum 90% Bayesian confidence interval (CI) was 21.1% (e.g. 13.7 % south, 90% CI 2.6 % – 23.0 %) and the median CI was 13.9%. Smaller north/south-ESAIM sets showed strong correlations with the 1441 set e.g. 384 ESAIMs (r2 = 0.970) (Figure S2). However, the smaller north/south-ESAIM sets showed somewhat broader confidence limits (e.g. 384 north/south ESAIM set showed maximum CI = 38.9% and a median CI = 17.1%. However, these differences are unlikely to affect most studies. The larger number of north/south-ESAIMs may be useful if a very homogeneous set of individuals of a particular ethnic group is desired for a specific study.

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