Combined results for new significant and suggestive GWAS signals: serum Gd-IgA1 levels were determined using HAA lectin-based ELISA, normalized and adjusted for age, case-control status and serum total IgA levels.

<p>Combined results for new significant and suggestive GWAS signals: serum Gd-IgA1 levels were determined using HAA lectin-based ELISA, normalized and adjusted for age, case-control status and serum total IgA levels.</p

Study cohorts after implementation of all quality control filters: the final counts of cases and controls by cohort are provided.

<p>Study cohorts after implementation of all quality control filters: the final counts of cases and controls by cohort are provided.</p

Genotypic effects and worldwide allelic frequency distribution for the two top genome-wide significant loci.

<p><b>(a)</b> Mean trait values (+/- standard errors) by rs13226913 genotype at the <i>C1GALT1</i> locus. (<b>b</b>) The distribution of rs13226913 alleles across the Human Genome Diversity Panel (HGDP) populations. <b>(c)</b> Mean trait values (+/- standard errors) by rs5910940 genotype at the <i>C1GALT1C1</i> locus. <b>(d)</b> The distribution of rs5910940 alleles across HGDP populations. The allelic distribution plots were modified from the HGDP Selection Browser. The trait values were expressed as standard normal residuals of log-transformed serum Gd-IgA1 levels after adjustment for age, serum total IgA levels, case-control status and cohort membership.</p

siRNA knock-down of C1GALT1, COSMC and COSMC+C1GALT1 in IgA1-secreting cell lines increases Gd-IgA1 production.

<p><b>(a)</b> knock-down in IgA1-secreting cell lines from healthy controls; mock-control (n = 5), non-targeting siRNA (n = 7), C1GALT1 siRNA (n = 5), COSMC siRNA (n = 7), and COSMC+C1GALT1 siRNA (n = 2); <b>(b)</b> knock-down in IgA1-secreting cell lines from IgAN patients; mock-control (n = 5), non-targeting siRNA (n = 7), C1GALT1 (n = 5), COSMC siRNA (n = 7), and COSMC+C1GALT1 siRNA (n = 2); <b>(c)</b> relative change in mRNA in IgA1-secreting cell lines after siRNA knock-down of C1GALT1 (n = 5), COSMC (n = 7), and COSMC+C1GALT1 (n = 2) compared to non-targeting siRNA control.</p

Longitudinal measurements of serum immunoglobulin levels and Gd-IgA1 levels over 4 years of follow-up.

<p>Initial and 4-year follow-up levels of <b>(a)</b> serum total IgG, <b>(b)</b> serum total IgA, and <b>(c)</b> serum Gd-IgA1 normalized for serum total IgA. Panels <b>(d, e, f)</b> represent scatter plots of initial (x-axis) versus follow-up (y-axis) values. P-values correspond to the Pearson’s test of correlation; r²: squared correlation coefficient.</p