CNV loci highly correlated with trait-associated SNPs.

<p>This table shows significant SNP-CNV pairs found in high LD. N stands for the number of CNV microarray markers correlated with the SNP genotypes, and r2CEU, r2YRI and r2CHBJPT stand for the linkage disequilibrium measures between the SNP and the CNV. Reported GWAS <i>P</i>-value is also shown together with a field indicating if the CNV association has been previously reported.</p

GStream method for SNP genotyping.

<p>This figure shows how GStream genotyping method works on two example markers, the first one representing a typical marker capturing a SNP (A and B) and the second one capturing both a SNP and a CNV (C and D). The leftmost graphs show the effects of the normalization procedure for the two markers, where the dotted blue lines enclose the ranges where candidate homozygotes and heterozygotes are identified in order to compute the scaling factors for each channel (black points over the axes). The rightmost graphs give an overview of the genotyping procedure: Upper subfigures represent the scaled BAF probability density function with the solid vertical lines setting the identified genotype centres, the dotted vertical lines setting the genotype limits and the horizontal lines representing the sequential search of genotype cluster peaks. Medium and lower subfigures represent genotype calls and quality call scores respectively.</p

GStream method for CNV genotyping.

<p>(A) Each CNV analysis is divided in four independent sets where the number of allele copies per channel intensity is estimated. Here, the homozygote intensities over its respective informative channels (upper rightmost and leftmost graphs) are fitted with a two-component model (in this case, capturing a deletion) while heterozygote intensities over each channel are better fitted with a one-component model (upper centre graphs). Lower graphs show the intensity distributions (solid black lines) together with the corresponding copy number score (red points) assigned to each sample. AA homozygotes are mostly classified as deletions (scores near to 1), BB homozygotes are divided into diploids (scores∼2) and deletions (scores∼1) while heterozygotes are classified as diploids (i.e. one allele detected at each channel). (B) Final representation of the analyzed probe where points represent samples and colour their relative copy number scores. SNP and CNV genotypes are assigned along the BAF and the intensity axis respectively.</p

Power to detect CNP associations.

A<p>CNV dataset provided by custom genotyping microarray-based studies.</p>B<p>CNV datasets provided by CGH-based studies.</p><p>Percentage of −log₁₀<i>P</i> ratios higher than 0.9 and lower than 1.1 over the CNV population-associated regions computed for each study. Platform difference refers to the percentage differences between HumanOmni1-Quad and Human1M-Duo platforms.</p

Public microarray data used in this study.

<p>The used microarray data comes from four different Illumina BeadChip platforms and the sample data comes from three HapMap populations. The total number of autosomal markers and the number of markers used for SNP genotyping evaluation are shown.</p

CNV regions for each dataset and platform used to evaluate the power to detect genome-wide associations.

<p>N_CNVR refers to the number of CNV loci selected from each study. Coverage with at least one marker within the CNV loci of both platforms is very similar although the marker density differs considerably. N_ASSOCS column refers to the total number of associated regions for the three population tests detected over the golden standard calls.</p

Global accuracy results for SNP genotyping.

<p>Call rate refers to the percentage of called genotypes while the accuracy is computed as the number of correct genotypes over the number of called genotypes. Global accuracy summarizes both measurements by computing the number of correct genotypes over the total number of genotypes available within the golden standard dataset.</p

Evaluating SNP genotyping performance.

<p>Plots comparing SNP genotyping algorithms for each microarray platform are tested. The vertical axis represents the percentage of SNPs that are excluded from the accuracy calculation by the lowest quality score criteria. GStream performed better at all the drop rate levels in all the platforms. A high decrease in performance is observed for GenCall when drop rate values are lower than its uncall rate (i.e. ∼2% in Human610Quad).</p

Genotype frequencies of the <i>FCGR2A</i> polymorphism rs1801274 in anti-CCP positive RA patients according to the clinical response at week 12.

<p>^aFisher's exact test; ANTI-CCP: anti-citrullinated protein antibodies; OR: Odds ratio using allele G as reference.</p><p>Genotype frequencies of the <i>FCGR2A</i> polymorphism rs1801274 in anti-CCP positive RA patients according to the clinical response at week 12.</p

Epidemiological and Clinical Features of the Patient Study Cohort.

<p>Except where indicated otherwise, values are the mean ±SD. RF: rheumatoid factor; Anti-CCP: anti-citrullinated protein antibodies; DMARDs: disease-modifying antirheumatic drugs; ΔDAS28; delta DAS28 (DAS28 baseline—DAS28 endpoint); EULAR: European League Against Rheumatism response, where Good and Moderate EULAR responders were merged into a single Responder category.</p><p>Epidemiological and Clinical Features of the Patient Study Cohort.</p