Fig. 5

Dissection of complex pleiotropic patterns of recurrent CNVs at 16p13.11. A 16p13.11 genetic landscape. Coordinates of UK Biobank duplications (shades of blue; top) and deletions (shades of red; bottom) overlapping the maximal CNV region (CNVR delimited by vertical dashed lines) associated with epilepsy, kidney stones, hypertension, and alkaline phosphatase (ALP). CNVs are divided and colored according to five categories (cat1-5) to reflect recurrent breakpoints, with atypical CNVs in gray (Additional file 1: Note S6). Breakpoints reflect segmental duplications, represented with a gray gradient proportional to the degree of similarity. Middle: genomic coordinates of genes and DECIPHER GD. Inset: Overlap between ABCC6’s exonic structure and cat5 deletions. B, D, F, H Negative logarithm of association p-values of CNVs (dark gray; model in parenthesis; CNVR delimited by vertical dashed lines) with B epilepsy, D kidney stones, F hypertension, and H ALP and SNPs with B epilepsy [73], D kidney stones [74], calcium levels, and phosphate levels (y-axis; break: //); F hypertension and systolic blood pressure [75], and H ALP. Lead SNPs are labeled. Red horizontal dashed lines represent genome-wide thresholds for significance for CNV-GWAS (p ≤ 7.5 × 10⁻⁶) and SNP-GWAS (p ≤ 5 × 10⁻⁸). C, E, G Prevalence (± standard error) of C epilepsy, E kidney stones, and G hypertension according to 16p13.11 copy-number (CN) and CNV categories from A. P-values compare carriers of specific deletions (CN = 1) and duplications (CN = 3) to copy-neutral (CN = 2) individuals (two-sided Fisher test). Number of cases and samples sizes are indicated (N = cases/sample size). I ALP levels according to 16p13.11 CN and CNV category, shown as boxplots; outliers are not shown. P-values compare carriers of specific deletions (CN = 1) and duplications (CN = 3) to copy-neutral (CN = 2) individuals (two-sided t-test). Gray horizontal line represents median ALP value in non-carriers