The PP Amerindian admixture mapping region on chromosome 17.

<p>The left panel provides the admixture mapping results as two lines, with the blue line that crosses the genome-wide significance threshold (horizontal grey dashed line) representing results from the primary analysis and the other, green line, representing the results from the conditional analysis, and the association results in the same region as circles. Lines and points are given as -log(<i>p</i>-value, 10) against genomic positions. Filled triangles correspond to the SNPs used in the conditional analysis. The right panel provides the ancestry-specific effect allele frequencies (EAF) for each of the SNPs used in the conditional analysis, as estimated by ASAFE applied on the HCHS/SOL data set [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188400#pone.0188400.ref030" target="_blank">30</a>].</p

Selected variants in top admixture mapping association regions, and their association testing results in stratified BP GWAS (stratified by genetic analysis groups and followed by a step of meta-analysis across the groups).

<p>All admixture mapping hits here were in the analysis of Amerindian ancestry versus other ancestries. We provide the effect estimate (Effect) from both the admixture mapping (Ancestry effect), and association mapping, the frequency of the ancestry (Ancestry freq), and the frequencies of the variant in the Mexican (high Amerindian ancestry) and Cuban (low Amerindian ancestry) genetic analysis groups. Genomic positions are in human build 37. A1 is the effect (tested) allele, A2 is the other allele. Type refers to imputation: ‘g’ is genotyped, ‘i’ imputed. Info is a measure of imputation quality. ^<i>a</i> For SNP rs118163160, the association analysis results when restricted to the Mainland groups were effect = −2.85, SE = 0.69, <i>p</i>-value = 3.84E-05. <i>P</i>-value for heterogeneity of the effect across the genetic analysis groups was 0.001.</p

The MAP Amerindian admixture mapping region on chromosome 11.

<p>The left provides the admixture mapping results as two lines, with the blue line that crosses the genome-wide significance threshold (horizontal grey dashed line) representing results from the primary analysis and the other, green line, representing the results from the conditional analysis, and the association results in the same region as circles. Lines and points are given as -log(<i>p</i>-value, 10) against genomic positions. Filled triangles correspond to the SNPs used in the conditional analysis. The right panel provides the ancestry-specific effect allele frequencies (EAF) for each of the SNPs used in the conditional analysis, as estimated by ASAFE applied on the HCHS/SOL data set [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188400#pone.0188400.ref030" target="_blank">30</a>].</p

The MAP (and SBP) Amerindian admixture mapping region on chromosome 6.

<p>The left panel provides the admixture mapping results as two lines, with the blue line that crosses the genome-wide significance threshold (horizontal grey dashed line) representing results from the primary analysis and the other, green line, representing the results from the conditional analysis, and the association results in the same region as circles. Lines and points are given as -log(<i>p</i>-value, 10) against genomic positions. Filled triangles correspond to the SNPs used in the conditional analysis. The right panel provides the ancestry-specific effect allele frequencies (EAF) for each of the SNPs used in the conditional analysis, as estimated by ASAFE applied on the HCHS/SOL data set [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188400#pone.0188400.ref030" target="_blank">30</a>].</p

Top admixture association results in significant association regions.

<p>The lead LAI provides the coordinates of the most significant local ancestry interval in the region. Ancestry freq provides the proportion of intervals inferred as inherited from the tested ancestry across the 12,116 individuals (24,232 chromosome). Effect size, SE and <i>p</i>-values were estimated based on the linear model for the effect of the local ancestry count on the trait.</p

Results from replication testing of SNPs in significant admixture association regions in 2,347 Pima Indians.

<p>Genomic positions are in human build 37. A1 is the effect (tested) allele, A2 is the other allele. For each of HCHS/SOL and the replication study, we provide allele frequencies, estimated effect sizes, and <i>p</i>-values. For the replication study, <i>p</i>-values are one-sided as determined by the direction of association observed in the HCHS/SOL. For the HCHS/SOL frequencies we report “Amer freq”: the estimated allele frequency in the Amerindian ancestry in the HCHS/SOL, as estimated using ASAFE [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188400#pone.0188400.ref030" target="_blank">30</a>].</p

Association of red cell phenotypes with alpha-globin regulatory variant rs11248850, overall and by −α3.7 deletion status.

<p>Association of red cell phenotypes with alpha-globin regulatory variant rs11248850, overall and by −α3.7 deletion status.</p

Association of alpha thalassemia with risk of clinical complications in the Cooperative Study of Sickle Cell Disease (CSSCD), stratified by α-globin rs11865131 genotype.

<p>Association of alpha thalassemia with risk of clinical complications in the Cooperative Study of Sickle Cell Disease (CSSCD), stratified by α-globin rs11865131 genotype.</p

Functional assays for α-globin enhancer variants.

<p>Normalized activity (RNA barcode count divided by DNA barcode count) from the massively parallel reporter assay. The median of the entire library was set to 0; therefore an activity of 0 corresponds roughly to minP transcriptional levels. Only elements overlapping with the MCS-R2 element have robust regulatory activity in K562 cells. (<b>B</b>) Relative luciferase activity as compared to minP promoter for α-globin enhancer variants (rs11865131 and rs11248850). A significant allelic difference in enhancer activity is observed for rs11865131 (p = 6.91 x 10⁻³ for lower luciferase activity with A allele). (<b>C</b>) Allelic skew for rs11865131 from DNase I hypersensitivity (DHS) data in 46 heterozygous cell types previously identified in(37) and in erythroblasts only ***p<0.0001.</p

Association of red cell and other clinically relevant phenotypes with sickle cell trait, stratified by number of copies of alpha-globin -3.7 kb deletion.

<p>Association of red cell and other clinically relevant phenotypes with sickle cell trait, stratified by number of copies of alpha-globin -3.7 kb deletion.</p