Supplementary material for "Susceptibility Haplotypes in Non-Cystic Fibrosis Newborns with Elevated Immunoreactive Trypsinogen"

Introduction Cystic fibrosis (CF) represents the most prevalent life-threatening autosomal recessive disorder in Europe, primarily affecting the respiratory tract, exocrine pancreatic function, and lipid metabolism. Immunoreactive trypsinogen (IRT) quantification constitutes the first-tier test in neonatal CF screening programs; however, elevated IRT levels may also be detected in infants who do not develop CF, generating false-positive (FP) results. The biological basis underlying increased IRT in these cases remains poorly understood and may involve genetic determinants independent of CFTR. We hypothesized that a subset of infants with false-positive CF NBS may harbor genetic variants associated with pancreatic enzyme regulation or exocrine pancreatic biology, potentially contributing to elevated IRT despite the absence of CF Description This dataset comprises aggregated whole-exome sequencing (WES) data from 212 samples, aligned to the genome assembly GRCh38 (hg38). Variants were identified using GATK HaplotypeCaller (v4.1.9.0), normalized and annotated using Variant Effect Predictor (VEP, v113.0). Genotypes with low Depth of Coverage (DP < 8) or low genotype quality (GQ < 20) were set to missing. Variants were subsequently excluded if they showed a missingness rate (Fmiss) ≥20% in either group or a between-group difference in Fmiss exceeding 5%. Samples with high genotype missingness, excessive identity-by-descent (IBD), or ancestry discordant with the reference cohort based on principal component analysis (PCA) were exluded. Analyses were restricted to genes already known to be implicated in pancreatic diseases: CASR, CCL2, CEL, CELA3B, CFTR, CLDN2, CPA1, CTRB1, CTRB2, CTRC, CTSB, CXCL8, KRT18, KRT8, MORC4, PRSS1, PRSS2, RIPPLY1, SBDS, SPINK1, TRPV6. The annotated VCF file includes the following metrics, calculated separately for samples classified as false positives (FP; n = 94) and true negatives (TN; n = 118): AN_FP: Total number of alleles in called genotypes in FP AN_TN: Total number of alleles in called genotypes in TN AC_FP: Allele count in genotypes in FP AC_TN: Allele count in genotypes in TN AC_Hom_FP: Allele counts in homozygous genotypes in FP AC_Hom_TN: Allele counts in homozygous genotypes in TN AC_Het_FP: Allele counts in heterozygous genotypes in FP AC_Het_TN: Allele counts in heterozygous genotypes in TN AF_FP: Allele frequency in FP AF_TN: Allele frequency in TN