Inferred human tree.

<p>A. Maximum likelihood tree. Plotted is the maximum-likelihood tree. Populations are colored according to geographic location (black: archaic humans, red: Africa, brown: Middle East, green: Europe, blue: Central Asia, purple: America, orange: East Asia). The scale bar shows ten times the average standard error of the entries in the sample covariance matrix (). For analysis including Oceania, see Figures S11 and S12. B. Residual fit. Plotted is the residual fit from the maximum likelihood tree in A. We divided the residual covariance between each pair of populations and by the average standard error across all pairs. We then plot in each cell this scaled residual. Colors are described in the palette on the right. Residuals above zero represent populations that are more closely related to each other in the data than in the best-fit tree, and thus are candidates for admixture events.</p

Inferred dog tree.

<p>A. Maximum likelihood tree. Populations are colored according to breed type. Dark blue: wild canids, grey: ancient breeds, brown: spitz breeds, black: toy dogs, red: spaniels, maroon: scent hounds, dark red: working dogs, light green: herding dogs, light blue: mastiff-like dogs, purple: small terriers, orange: retrievers, dark green: sight hounds. The scale bar shows ten times the average standard error of the entries in the sample covariance matrix (). B. Residual fit. Plotted is the residual fit from the maximum likelihood tree in A. We divided the residual covariance between each pair of populations and by the average standard error across all pairs. We then plot in each cell this scaled residual. Colors are described in the palette on the right.</p

Inferred dog graph.

<p>Plotted is the structure of the graph inferred by <i>TreeMix</i> for dog populations, allowing ten migration events. Migration arrows are colored according to their weight. The scale bar shows ten times the average standard error of the entries in the sample covariance matrix (). See the main text for discussion. The residual fit from this graph is presented in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002967#pgen.1002967.s013" target="_blank">Figure S13</a>.</p

Inferred human tree with mixture events.

<p>Plotted is the structure of the graph inferred by <i>TreeMix</i> for human populations, allowing ten migration events. Migration arrows are colored according to their weight. Horizontal branch lengths are proportional to the amount of genetic drift that has occurred on the branch. The scale bar shows ten times the average standard error of the entries in the sample covariance matrix (). The residual fit from this graph is shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002967#pgen.1002967.s009" target="_blank">Figure S9</a>. Admixture from Neandertals to non-African populations is only apparent when considering subsets of the data (see Discussion and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002967#pgen.1002967.s015" target="_blank">Figure S15</a>).</p

Expression QTN distribution estimated using only those Affymetrix probes that are located within the same exon as an Illumina probe creates an apparent 3′ signal peak.

<p>Overall, the Affymetrix probes are spread roughly evenly across exons while the Illumina probes are 3′ biased. By analyzing only those Affymetrix probes that are in the same exons as Illumina probes, we create an apparent 3′ signal peak. For the sake of comparison, the grey line represents the original distribution as plotted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030629#pone-0030629-g001" target="_blank">Figure 1</a>.</p

Illumina last exon expression-QTLs are more likely to be splicing-QTLs.

<p>We determined the most significant SNP for each Illumina eQTL, and then tested every such SNP for association at the gene- and exon-levels using the Affymetrix and RNA-seq data. Here we show QQ-plots for these Illumina eQTNs in the exon-level analysis (left) and the gene-level analysis (right), using the Affymetrix exon array data (top) and RNA-seq data (bottom). The color codes correspond to 5 exclusive categories of the Illumina eQTNs with respect to the target gene: intragenic, exonic “(first, internal and last) or intronic (intron). Note that last-exon Illumina eQTNs tend to replicate well at the exon level, but poorly at the gene level, suggesting that these are frequently exon-QTLs but infrequently gene-QTLs.</p

eQTN enrichment within exons is strongly supported by all three datasets while there is relatively weak evidence that the last exon is special.

<p>The table displays the odds ratio estimates together with their corresponding 95% confidence intervals, as estimated by the empirical Bayesian model (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030629#s4" target="_blank">Methods</a>) for each expression dataset (Illumina, Affymetrix, RNA-seq). Model 1 (TSS, intragenic) estimates the odds ratio that a SNP inside the transcribed region is an eQTN compared to a SNP outside the transcribed region (controlling for distance from TSS). For Model 2 (TSS, intron, exon) and Model 3 (TSS, intron, exon, last exon) we used the intron annotation as the reference: the reported exon and last exon odds ratio can then be interpreted as the relative odds that a SNP within these regions is an eQTN with respect to an intron SNP at the same distance from the TSS.</p

Expression QTN distributions estimated using three different technologies for measuring gene expression.

<p>The left-hand column plots the distribution of locations of most significant SNPs for each technology; the red arrows indicate the location of the TES peak observed in the Illumina data. SNPs outside genes are assigned to bins based on their physical distance from the TSS (for upstream SNPs), or TES (downstream SNPs). SNPs inside genes are assigned to bins based on their fractional location within the gene. The plotted gene size is the average gene length in the data. To provide a formal comparison among different models, the right-hand column displays the difference in Akaike Information Criterion (AIC) values between different parameterizations of our Bayesian hierarchical model (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030629#s4" target="_blank">Methods</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030629#pone-0030629-t001" target="_blank">Table 1</a>). Small values of “(AIC”) indicate better model fit, and the best model for each data set is indicated with a horizontal arrow. The labels for the four models indicate the different parameters included in each model: “TSS” refers to our basic distance model measured as distance from TSS; “intragenic” means that we use a single additional parameter for all SNPs within the transcript; “exon, intron” indicates that we use separate parameters for exonic and intronic SNPs respectively, and “last exon” indicates that we add an additional parameter for SNPs in the final exon.</p

Testing for the influence of single genetic variants on age-specific mortality in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort.

<p>(A) Manhattan plot of <i>P</i> values for the change in allele frequency with age. The red line marks the <i>P</i> = 5 × 10⁻⁸ threshold. (B) Allele frequency trajectory of rs6857, a tag SNP for the <i>APOE ε</i>4 allele, with age. Data points are the frequencies of the risk allele within 5-year interval age bins (± 2 SE), with the center of the bin indicated on the x-axis (except for the first and the last points). Bins with ages below 38 years are merged into 1 bin because of the relatively small sample sizes. The dashed line shows the expected frequency based on the null model, accounting for confounding batch effects and changes in ancestry (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#sec007" target="_blank">Materials and methods</a>). In orange are the mean ages at onset of Alzheimer disease for carriers of 0, 1, or 2 copies of the <i>APOE ε</i>4 allele [<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.ref053" target="_blank">53</a>]. See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.s035" target="_blank">S1 Data</a> for underlying data.</p

Testing for the influence of sets of trait-associated variants on survival of the mothers of UK Biobank participants.

<p>(A) Quantile-quantile plot for association between the polygenic score of 42 traits (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.s030" target="_blank">S1 Table</a>) with mother’s survival, using the Cox model. The red line indicates the distribution of the <i>P</i> values under the null. Signs “+” and “−” indicate protective and detrimental effects associated with higher values of polygenic scores, respectively. See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.s031" target="_blank">S2 Table</a> for <i>P</i> values and hazard ratios for all traits. (B–F) Trajectory of polygenic score with age at death of mothers for top traits associated with maternal survival (only independent signals are shown, see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.s020" target="_blank">S20 Fig</a>): puberty timing (B), age at first birth (AFB) (C), coronary artery disease (CAD) (D), low-density lipoproteins (LDL) (E), and high-density lipoproteins (HDL) (F). Data points in (B–F) are mean polygenic scores within 5-year interval age bins (± 2 SE), with the center of the bin indicated on the x-axis (except for the first and the last points). The dashed line shows the expected score based on the null model, accounting for confounding batch effects, changes in ancestry, and participant’s age, sex, year of birth, and the Townsend index (a measure of socioeconomic status). See <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002458#pbio.2002458.s036" target="_blank">S2 Data</a> for underlying data.</p