Genetic Correlations Among Corneal Biophysical Parameters and Anthropometric Traits

Overview

Journal Transl Vis Sci Technol

Specialties Biomedical Engineering
Ophthalmology

Date 2023 Aug 10

PMID 37561511

Authors

Henry C Cousins

Clara C Cousins

Girish Valluru

Russ B Altman

Yutao Liu

Louis R Pasquale

Sumayya Ahmad

Affiliations

Soon will be listed here.

Abstract

Purpose: The genetic architecture of corneal dysfunction remains poorly understood. Epidemiological and clinical evidence suggests a relationship between corneal structural features and anthropometric measures. We used global and local genetic similarity analysis to identify genomic features that may underlie structural corneal dysfunction.

Methods: We assembled genome-wide association study summary statistics for corneal features (central corneal thickness, corneal hysteresis [CH], corneal resistance factor [CRF], and the 3 mm index of keratometry) and anthropometric traits (body mass index, weight, and height) in Europeans. We calculated global genetic correlations (rg) between traits using linkage disequilibrium (LD) score regression and local genetic covariance using ρ-HESS, which partitions the genome and performs regression with LD regions. Finally, we identified genes located within regions of significant genetic covariance and analyzed patterns of tissue expression and pathway enrichment.

Results: Global LD score regression revealed significant negative correlations between height and both CH (rg = -0.12; P = 2.0 × 10-7) and CRF (rg = -0.11; P = 6.9 × 10-7). Local analysis revealed 68 genomic regions exhibiting significant local genetic covariance between CRF and height, containing 2874 unique genes. Pathway analysis of genes in regions with significant local rg revealed enrichment among signaling pathways with known keratoconus associations, including cadherin and Wnt signaling, as well as enrichment of genes modulated by copper and zinc ions.

Conclusions: Corneal biophysical parameters and height share a common genomic architecture, which may facilitate identification of disease-associated genes and therapies for corneal ectasias.

Translational Relevance: Local genetic covariance analysis enables the identification of associated genes and therapeutic targets for corneal ectatic disease.

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