Data_Sheet_2_Re-analysis of Whole Genome Sequence Data From 279 Ancient Eurasians Reveals Substantial Ancestral Heterogeneity.DOCX

<p>Supervised clustering or projection analysis is a staple technique in population genetic analysis. The utility of this technique depends critically on the reference panel. The most commonly used reference panel in the analysis of ancient DNA to date is based on the Human Origins array. We previously described a larger reference panel that captures more ancestries on the global level. Here, I reanalyzed DNA data from 279 ancient Eurasians using our reference panel. I found substantially more ancestral heterogeneity than has been reported. Reanalysis provides evidence against a resurgence of Western hunter-gatherer ancestry in the Middle to Late Neolithic and evidence for a common ancestor of farmers characterized by Western Asian ancestry, a transition of the spread of agriculture from demic to cultural diffusion, at least two migrations between the Pontic-Caspian steppes and Bronze Age Europe, and a sub-Saharan African component in Natufians that localizes to present-day southern Ethiopia.</p

Table_1_Re-analysis of Whole Genome Sequence Data From 279 Ancient Eurasians Reveals Substantial Ancestral Heterogeneity.XLSX

<p>Supervised clustering or projection analysis is a staple technique in population genetic analysis. The utility of this technique depends critically on the reference panel. The most commonly used reference panel in the analysis of ancient DNA to date is based on the Human Origins array. We previously described a larger reference panel that captures more ancestries on the global level. Here, I reanalyzed DNA data from 279 ancient Eurasians using our reference panel. I found substantially more ancestral heterogeneity than has been reported. Reanalysis provides evidence against a resurgence of Western hunter-gatherer ancestry in the Middle to Late Neolithic and evidence for a common ancestor of farmers characterized by Western Asian ancestry, a transition of the spread of agriculture from demic to cultural diffusion, at least two migrations between the Pontic-Caspian steppes and Bronze Age Europe, and a sub-Saharan African component in Natufians that localizes to present-day southern Ethiopia.</p

Data_Sheet_1_Re-analysis of Whole Genome Sequence Data From 279 Ancient Eurasians Reveals Substantial Ancestral Heterogeneity.DOCX

<p>Supervised clustering or projection analysis is a staple technique in population genetic analysis. The utility of this technique depends critically on the reference panel. The most commonly used reference panel in the analysis of ancient DNA to date is based on the Human Origins array. We previously described a larger reference panel that captures more ancestries on the global level. Here, I reanalyzed DNA data from 279 ancient Eurasians using our reference panel. I found substantially more ancestral heterogeneity than has been reported. Reanalysis provides evidence against a resurgence of Western hunter-gatherer ancestry in the Middle to Late Neolithic and evidence for a common ancestor of farmers characterized by Western Asian ancestry, a transition of the spread of agriculture from demic to cultural diffusion, at least two migrations between the Pontic-Caspian steppes and Bronze Age Europe, and a sub-Saharan African component in Natufians that localizes to present-day southern Ethiopia.</p

L'Écho : grand quotidien d'information du Centre Ouest

15 janvier 19431943/01/15 (A72,N395).Appartient à l’ensemble documentaire : PoitouCh

Transferability of genome-wide associated loci for asthma in African Americans

<p><i>Objective:</i> Transferability of significantly associated loci or GWAS “hits” adds credibility to genotype-disease associations and provides evidence for generalizability across different ancestral populations. We sought evidence of association of known asthma-associated single nucleotide polymorphisms (SNPs) in an African American population. <i>Methods:</i> Subjects comprised 661 participants (261 asthma cases and 400 controls) from the Howard University Family Study. Forty-eight SNPs previously reported to be associated with asthma by GWAS were selected for testing. We adopted a combined strategy by first adopting an “exact” approach where we looked-up only the reported index SNP. For those index SNPs missing form our dataset, we used a “local” approach that examined all the regional SNPs in LD with the index SNP. <i>Results:</i> Out of the 48 SNPs, our cohort had genotype data available for 27, which were examined for exact replication. Of these, two SNPs were found positively associated with asthma. These included: rs10508372 (OR = 1.567 [95%CI, 1.133-2.167], <i>P</i> = 0.0066) and rs2378383 (OR = 2.147 [95%CI, 1.149–4.013], <i>P</i> = 0.0166), located on chromosomal bands 10p14 and 9q21.31, respectively. Local replication of the remaining 21 loci showed association at two chromosomal loci (9p24.1-rs2381413 and 6p21.32-rs3132947; Bonferroni-corrected <i>P</i> values: 0.0033 and 0.0197, respectively). Of note, multiple SNPs in LD with rs2381413 located upstream of <i>IL33</i> were significantly associated with asthma. <i>Conclusions:</i> This study has successfully transferred four reported asthma-associated loci in an independent African American population. Identification of several asthma-associated SNPs in the upstream of the <i>IL33</i>, a gene previously implicated in allergic inflammation of asthmatic airway, supports the generalizability of this finding.</p

Multiple Loci Associated with Renal Function in African Americans

<div><p>The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in <em>APOL1</em> associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry <em>vs</em>. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.</p> </div

Effect of the number of individuals per subpopulation on bias.

<p>The x-axis shows the number of individuals per subpopulation. The y-axis shows the mean (left) and variance (right) of </p><p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mn>1</mn></p><p></p><p></p><p></p><p></p><p></p> (red), <p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mn>2</mn></p><p></p><p></p><p></p><p></p><p></p> (blue), <p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mi>m</mi></p><p></p><p></p><p></p><p></p><p></p> (green), and <p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mn>3</mn></p><p></p><p></p><p></p><p></p><p></p> (orange) values, given <i>F</i>_<i>st</i> = 0.5 and an average allele frequency <i>p</i> = 0.2. From top to bottom, the plots represent the number of subpopulations <i>r</i> = 10, 20, and 40, respectively.<p></p

F^st between WETH and HapMap 3 samples.

<p>* Shown are means (variances) of </p><p></p><p></p><p></p><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi><mi>t</mi></p><p></p><p></p><p></p><p></p>.<p></p><p></p><p></p><p></p><p></p><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi><mi>t</mi></p><p></p><p></p><p></p><p></p> between WETH and HapMap 3 samples.<p></p

F^st vs. <i>F</i>_<i>st</i> and ϑ^2 for two subpopulations.

<p></p><p></p><p></p><p></p><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi><mi>t</mi></p><p></p><p></p><p></p><p></p> vs. <i>F</i>_<i>st</i> and <p></p><p></p><p></p><p></p><p><mi>ϑ</mi><mo>^</mo></p><mn>2</mn><p></p><p></p><p></p><p></p> for two subpopulations.<p></p

Effect of the number of subpopulations on bias.

<p>The x-axis shows the number of subpopulations. The y-axis shows the mean (left) and variance (right) of </p><p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mn>1</mn></p><p></p><p></p><p></p><p></p><p></p> (red), <p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mn>2</mn></p><p></p><p></p><p></p><p></p><p></p> (blue), <p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mi>m</mi></p><p></p><p></p><p></p><p></p><p></p> (green), and <p></p><p></p><p></p><p><mi>F</mi></p><p><mi>s</mi><mi>t</mi></p><p></p><mo>−</mo><p></p><p><mi>F</mi><mo>^</mo></p><p><mi>s</mi></p><p><mi>t</mi><mn>3</mn></p><p></p><p></p><p></p><p></p><p></p> (orange) values, given <i>F</i>_<i>st</i> = 0.5 and average allele frequency <i>p</i> = 0.2. The top plot represents 5 individuals per subpopulation and the bottom plot represents 1000 individuals per subpopulation.<p></p