Biology subjects

Byrne, E. M.

Publications and source records attributed to Byrne, E. M..

7 recordsLinked to original sources

bioRxiv2026

Retinal resuscitation in post-mortem eyes

Vision loss compromises the quality of life of millions of people worldwide. Currently, vision-restoring therapies are lacking. Post-mortem preservation of human eyes may enable whole eye transplantation (WET) or therapeutic development. We developed an approach to cannulate the ophthalmic artery and perfuse post-mortem pig and human eyes using a custom-built device, Eye-in-Care-Box (ECaBox). Retinal vasculature imaging and reconstruction were used to assess perfusion efficacy using a supervised deep learning model. Without intervention, the retina degrades post-mortem, whereas perfusion preserves retinal structure and cell viability for up to 24-hours. Eyes were perfused within 30 minutes post-extraction, and regained light-responses persisted for up to 10 hours after death, challenging the notion that response to light ends at death. Our findings show that intact eyes can be resuscitated and preserved outside the body, supporting the ECaBox platform for WET preservation and pre-clinical therapeutic testing. Ultimately, ECaBox may bring vision-restoring treatments to patients.

neuroscience↗

bioRxiv2019

Genome-wide association study of gastrointestinal disorders reinforces the link between the digestive tract and the nervous system

Genetic factors are recognized to contribute to common gastrointestinal (GI) diseases such as gastro-oesophageal reflux disease (GORD), peptic ulcer disease (PUD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We conducted genome-wide association analyses based on 456,414 individuals and identified 27 independent and significant loci for GORD, PUD and IBS, including SNPs associated with PUD at or near genes MUC1, FUT2, PSCA and CCKBR, for which there are previously established roles in Helicobacter pylori infection, response to counteract infection-related damage, gastric acid secretion and gastrointestinal motility. Post-GWAS analyses implicate putative functional links between the nervous system and gastrointestinal tract for GORD, PUD and IBS, including the central nervous system, the enteric nervous system and their connection. Mendelian Randomisation analyses imply potentially bi-directional causality (the risk of GORD in liability to major depression and the risk of major depression in liability to GORD) or pleiotropic effect between them. A stronger genetic similarity among GORD, PUD and IBS than between these disorders and IBD is reported. These findings advance understanding the role of genetic variants in the etiology of GORD, PUD and IBS and add biological insights into the link between the nervous system and the gastrointestinal tract.

genomics↗

bioRxiv2019

Insights into the aetiology of snoring from observational and genetic investigations in the UK Biobank (n=408,317)

We conducted the largest study of snoring using data from the UK Biobank (n [~] 408,000; snorers [~]152,000). A genome-wide association study (GWAS) identified 42 genome-wide significant loci, with a SNP-based heritability estimate of [~]10% on the liability scale. Genetic correlations with body mass index, alcohol intake, smoking, schizophrenia, anorexia nervosa and neuroticism were observed. Gene-based associations identified 173 genes, including DLEU7, MSRB3 and POC5 highlighting genes expressed in brain, cerebellum, lungs, blood, and oesophagus tissues. We used polygenic scores (PGS) to predict recent snoring and probable obstructive sleep apnoea (OSA) in an independent Australian sample (n[~]8,000). Mendelian randomisation analyses provided evidence that larger whole body fat mass causes snoring. Altogether, our results uncover new insights into the aetiology of snoring as a complex sleep-related trait and its role in health and disease beyond being a cardinal symptom of OSA.

genomics↗

bioRxiv2019

The Australian Genetics of Depression Study: Study Description and Sample Characteristics

ObjectivesDepression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression, and to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. This paper describes the recruitment and characteristics of the sample.\n\nMethodsParticipants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form, and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample were sent a saliva kit in the mail.\n\nResultsA total of 20,689 participants, 75% of whom were female, enrolled in the study. The average age of participants was 43 years {+/-} 15 years. 15,807 participants (76% of the participant group) returned saliva kits. The overwhelming majority of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a depressive episode. Rates of comorbidity with other psychiatric disorders were high. Two-thirds of the sample reported having taken more than one type of antidepressant during treatment for their depression.\n\nConclusionsThis study was effective in recruiting a large community sample of people with a history of clinical depression, highlighting the willingness of Australians to engage with medical research. A combination of recruitment through health records and media as well as use of an online questionnaire made it feasible to recruit the large sample needed for investigating the genetics of common diseases. It will be a valuable resource for investigating risk factors for depression, treatment response to antidepressants and susceptibility to side effects.

genetics↗

bioRxiv2018

Genetic analyses of medication-use and implications for precision medicine

It is common that one medication is prescribed for several indications, and conversely that several medications are prescribed for the same indication, suggesting a complex biological network for disease risk and its relationship with pharmacological function. Genome-wide association studies (GWASs) of medication-use may contribute to understanding of disease etiology, generation of new leads relevant for drug discovery and quantify prospects for precision medicine. We conducted GWAS to profile self-reported medication-use from 23 categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that met stringent criteria for statistical significance were identified. We investigated the implications of these GWAS findings in relation to biological mechanism, drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes were 16 known therapeutic-effect target genes for medications from 9 categories.

genetics↗

bioRxiv2018

Genome-wide meta-analysis of depression in 807,553 individuals identifies 102 independent variants with replication in a further 1,507,153 individuals

Major depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.

genetics↗

bioRxiv2018

Genome-wide association analyses of chronotype in 697,828 individuals provides new insights into circadian rhythms in humans and links to disease

Using genome-wide data from 697,828 research participants from 23andMe and UK Biobank, we increase the number of identified loci associated with being a morning person, a behavioural indicator of a persons underlying circadian rhythm, from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we show that the chronotype loci influence sleep timing: the mean sleep timing of the 5% of individuals carrying the most "morningness" alleles was 25 minutes earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. We provide evidence that being a morning person is causally associated with better mental health but does not appear to affect BMI or Type 2 diabetes. This study offers new insights into the biology of circadian rhythms and links to disease in humans.

genetics↗