Publications by authors named "Pirro Hysi"

Purpose: Use of genome-wide association studies (GWASs) in combination with transcriptomic arrays of different tissues or cell lines can reveal relevant cellular profiles and significantly improve understanding of the mechanisms of diseases. However, due to difficulty of access, few ocular transcriptomics datasets are available. This work aimed to create and make available an expression library platform that can be used with popular and versatile tools such as the linkage disequilibrium score (LDSC) regression techniques to identify specific cell lines enriched in ocular diseases.

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Purpose: To report findings in GUCA1A-associated retinopathy, a rare autosomal-dominant retinopathy.

Methods: Clinical features and investigations from molecularly confirmed patients at a large referral center were analyzed (retrospective cohort study).

Results: Nineteen patients (14 families), with five different variants, were included: p.

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A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study in the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic risk individuals existed.

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High intraocular pressure (IOP) is an important risk factor for glaucoma, which is influenced by genetic and environmental factors. However, the etiology of high IOP remains uncertain. Metabolites are compounds involved in metabolism which provide a link between the internal (genetic) and external environments.

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Refractive error (RE) and myopia are complex polygenic conditions with the majority of genome-wide associated genetic variants in non-exonic regions. Given this, and the onset during childhood, gene-regulation is expected to play an important role in its pathogenesis. This prompted us to explore beyond traditional gene finding approaches.

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  • * By analyzing data from the Million Veteran Program and other cohorts, the study identifies 63 genetic loci linked to AMD, including 30 that were previously unknown, highlighting significant differences in risk among various ancestries.
  • * The findings reveal that certain genetic risk factors, like those found in the CFH locus, have varying effects based on ancestry, suggesting that targeted therapies could be developed by considering these genetic differences.
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  • - Chronic widespread pain (CWP) is linked to increased arterial stiffness and carotid plaque, indicating a potential risk for cardiovascular disease, as observed in a study with around 3000 participants from TwinsUK.
  • - Genetic factors account for a significant portion of the variations in CWP and its cardiovascular implications, with twin modeling revealing shared pathways between CWP, arterial stiffness, and plaque presence.
  • - The study also suggests a causal relationship between CWP and coronary artery disease, implying that individuals with CWP may face heightened cardiovascular risks partly due to genetic influences.
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  • * A multi-ethnic meta-analysis revealed 22 risk loci linked to NTG, with 17 of these not previously identified, including significant new associations with BMP4 and TBKBP1.
  • * Findings suggest there’s a genetic overlap in risk factors between NTG and HTG, but NTG shows a generally lower risk effect, pointing to the potential for immunomodulatory treatments as neuroprotective options for glaucoma.
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Purpose: One of the strongest genetic associations with myopia is near the GJD2 gene. Recently, this locus was associated with cone-driven electroretinograms (ERGs), with findings highlighting OFF pathway signals specifically. The ERG i-wave is thought to originate in retinal OFF pathways.

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Objectives: Maternal self-reported ethnicity is recognised as a risk factor for pre-eclampsia in clinical screening tools and models. This study investigated whether ethnicity is acting as a proxy for genetic variants in this context.

Study Design: A total of 436 women from multi-ethnic backgrounds recruited to two UK observational pregnancy hypertension cohort studies were genotyped.

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Purpose: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis.

Design: Two-sample MR analysis.

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Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes.

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Article Synopsis
  • The study analyzed whole genome sequencing data from 1,751 individuals in the UK and 2,587 subjects from Qatar.
  • Researchers found an association between rare variants in the sour taste gene KCNJ2 and lower levels of low-density lipoprotein cholesterol (LDL-C) and a 22% reduction in dietary trans-fat intake.
  • This discovery highlights a potential new genetic factor that could influence LDL-C levels, which is important for understanding cardiovascular disease risks.
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Purpose: We sought to explore whether sex imbalances are discernible in several autosomally inherited macular dystrophies.

Methods: We searched the electronic patient records of our large inherited retinal disease cohort, quantifying numbers of males and females with the more common (non-ABCA4) inherited macular dystrophies (associated with BEST1, EFEMP1, PROM1, PRPH2, RP1L1, and TIMP3). BEST1 cases were subdivided into typical autosomal dominant and recessive disease.

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Background: Amblyopia is a common neurodevelopmental condition and leading cause of childhood visual impairment. Given the known association between neurodevelopmental impairment and cardiometabolic dysfunction in later life, we investigated whether children with amblyopia have increased risk of cardiometabolic disorders in adult life.

Methods: This was a cross-sectional and longitudinal analysis of 126,399 United Kingdom Biobank cohort participants who underwent ocular examination.

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Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1.

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Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability.

Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans.

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Purpose: Smoking may influence measured IOP through an effect on corneal biomechanics, but it is unclear whether this factor translates into an increased risk for glaucoma. This study aimed to examine the association of cigarette smoking with corneal biomechanical properties and glaucoma-related traits, and to probe potential causal effects using Mendelian randomization (MR).

Methods: Cross-sectional analyses within the UK Biobank (UKB) and Canadian Longitudinal Study on Aging (CLSA) cohorts.

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  • Researchers conducted a study to identify genetic factors influencing the likelihood of women giving birth to spontaneous dizygotic (DZ) twins, uncovering four new loci: GNRH1, FSHR, ZFPM1, and IPO8, alongside previously known loci FSHB and SMAD3.
  • * The study involved a large genome-wide association meta-analysis (GWAMA) of over 700,000 participants, focusing on mothers of spontaneous DZ twins and their offspring, excluding cases from assisted reproductive technologies (ARTs).
  • * Findings indicate that the newly identified loci play roles in female reproduction, and significant correlations were found with various reproductive traits and body size, suggesting evolutionary pressures against DZ twinning in humans.
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Purpose: Changes in refractive error during young adulthood is common yet risk factors at this age are largely unexplored. This study explored risk factors for these changes, including gene-environmental interactions.

Methods: Spherical equivalent refraction (SER) and axial length (AL) for 624 community-based adults were measured at 20 (baseline) and 28 years old.

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Purpose: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is selectively lost, a negative waveform might represent the response of the dark-adapted cone system.

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Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel).

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Although glaucoma is a disease modulated by eye pressure, the mechanisms of pressure sensing in the eye are not well understood. Here, we investigated associations between mechanosensitive ion channel gene variants and primary open-angle glaucoma (POAG). Common (minor allele frequency > 5%) single nucleotide polymorphisms located within the genomic regions of 20 mechanosensitive ion channel genes in the K2P, TMEM63, PIEZO and TRP channel families were assessed using genotype data from the NEIGHBORHOOD consortium of 3853 cases and 33,480 controls.

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