Deletion at the chr15q13.1–13.3 locus in a language impaired proband.

<p>(A) A snapshot from the UCSC Genome Browser (<a href="http://genome.ucsc.edu/" target="_blank">http://genome.ucsc.edu/</a>; hg19) showing the genomic region encompassed by the chr15q13.1–13.3 deletion identified in a child with language impairment. The tracks at the bottom indicate the breakpoints previously mapped at this region (BP3; BP4 and BP5); the deletion predictions by QuantiSNP, PennCNV and by merging the two algorithms; and the location of the six amplicons used for validation. (B) qPCR results for the six amplicons in the proband’s family (colour coded bars indicate: father in green; mother in red; proband in blue and sibling in orange; the reference in grey). Approximately 50% reduction in copy number at amplicons 2–5 in the proband relative to reference and family members indicates a <i>de novo</i> deletion occurring at BP3-BP5.</p

P-values from single-SNP analyses for VIQ and PIQ in replication samples.

<p>p-values statistically significant are in bold.</p><p>RA = Risk alleles are given only for results showing trend of association (p<0.1); NT = not tested.</p><p>Risk allele was G for all SNPs in all samples.</p

The intronic marker rs7182874 (ancestral allele = C; derived, minor allele = T) within the gene <i>PCSK6</i> on chromosome 15 is associated with relative hand skill in individuals with reading disability.

<p>β = effect size of each copy of the minor allele in standard deviations, S.E. = Standard Error.</p

LR asymmetry genes are associated with relative hand skill (meta-analysis of cohorts 1–3).

<p>We've listed the ten lowest gene <i>P</i> values that are also within one of the four enriched phenotypes from <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003751#pgen-1003751-t004" target="_blank"><b>Table 4</b></a> in the RD meta-analysis. MAF = minor allele frequency, β = effect size of each copy of the minor allele, in standard deviations.</p

Summary results for rs917235/rs714939 haplotype associations with VIQ in the ALSPAC cohort.

<p>p-values statistically significant are in bold.</p

Imaging results.

<p>(A) Main association of rs917235 with white matter volume. Sagittal view of the significant cluster associated with rs917235 at the MNI coordinates of X = −13, −8, 8, and 13 mm relative to the midline. The background image is the average of all individuals' white matter segmented images. The colour-bar shows the z-scores of the statistical analysis. (B–D) Structural connectivity. (B) A sample of fiber tracking from one individual passing through the region associated with rs917235. Different colours show the direction of pathways (red for left-right, blue for superior-inferior, and green for anterior-posterior). (C) Overlay of tract tracing from 30 randomly selected individuals. The colour-bar is a count for the number of subjects; yellow shows the most probable pathways. (D) Cortical end-points of the white matter pathways showing that the fibers connect right postcentral gyrus, superior parietal lobule, precuneous, occipital cortex and temporal fusiform gyrus to the analogous left regions.</p

Details of phenotypic measures.

<p>VIQ (verbal IQ); PIQ (performance (non-verbal) IQ); SD (standard deviation); WISC (Wechsler Intelligence Scale for Children); BAS (British Abilities Scales); WAIS (Wechsler Adult Intelligence Scale); PPVT (Peabody Picture Vocabulary Test); RCPM (Raven's Coloured Progressive Matrices).</p

GWAS study design.

<p>Three cohorts with reading disability and a further general population cohort were genotyped and tested after imputation for association with relative hand skill.</p