Fig 1.
The overview of the study based on 514,050 individuals in the UK Biobank and FinnGen cohorts.
We identified the association between ANGPTL7 and intraocular pressure (IOP) phenotypes using the genome-wide association analysis for rare (0.01% < MAF < 1%) protein-altering variants outside of MHC region in UK Biobank and applied burden and dispersion test (Analysis 1). In FinnGen, we discovered a Finnish enriched allele, p.Arg220Cys, in ANGPTL7 and performed association and subtype analysis of glaucoma (Analysis 2). In the UK Biobank, we replicated the associations between ANGPTL7 and glaucoma using the individuals that are not included in Analysis 1 (Analysis 3). OR corresponds to the odds ratio.
Table 1.
ANGPTL7 IOP protein-altering variant association in UK Biobank.
The association statistics for corneal compensated IOP and Goldman-correlated IOP are shown. Variant includes chromosome, position, reference, and alternate allele (hg19). rsID—the rs identifier of the genetic variant. HGVSp—the HGVS amino acid nomenclature. MAF—the minor allele frequency in UK Biobank white British population. Beta—estimated regression coefficient with 95% confidence intervals. P—p-value of association.
Table 2.
ANGPTL7 allelic series association summary in UK Biobank and FinnGen.
Variant: the rs identifier (rsID), the amino acid nomenclature (HGVSp), and genomic coordinate (CHR for chromosome and POS for the position in hg19), as well as reference (REF) and alternate (ALT) alleles, are shown. Dosage—genotype of individuals for protein and nucleotide sequences. Carrier frequency—carrier frequency in UK Biobank (UK) and FinnGen (Finland) for the respective genotype dosage. N with IOP—number of individuals in UK Biobank with intraocular pressure measurements corresponding to the genotype dosage. Effect size estimates—reported effect size estimates. IOP (mmHg) [95% CI]—unstandardized estimates of effect size on corneal-compensated and Goldmann-correlated intraocular pressure measurements (NB: standardized estimated effect sizes may have lower p-values due to normalization procedure). OR for glaucoma—estimate odds ratio on glaucoma risk for the respective genotype dosage. NS non-significant (p > 0.1). Effect sizes always reported with respect to alternate allele dosage.