Objective: The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 ( ACTN4/CAPN12 ) for retinal venular tortuosity ( TortV ), and one at 13q34 ( COL4A2 ) for retinal arteriolar tortuosity ( TortA ); these 2 loci were subsequently confirmed in 3 independent cohorts (N total =1413). In the combined analysis of discovery and replication cohorts, the lead single-nucleotide polymorphism in ACTN4 / CAPN12 was rs1808382 (β s.d. =-0.109; SE=0.015; P =2.39×10- 13 ) and in COL4A2 was rs7991229 (β s.d. =0.103; SE=0.015; P =4.66×10- 12 ). Notably, the ACTN4 / CAPN12 locus associated with TortV is also associated with coronary artery disease, heart rate, and atrial fibrillation. Conclusions: Genetic determinants of retinal vascular tortuosity are also linked to cardiovascular health. These findings provide a molecular pathophysiological foundation for the use of retinal vascular traits as biomarkers for cardiovascular diseases.

Objective: The COVID-19 pandemic has had a profound effect on global mental health, with one-third of infected individuals developing a psychiatric or neurological disorder 6 months after infection. The risk of infection and the associated restrictions introduced to reduce the spread of the virus have also impacted help-seeking behaviours. Therefore, this study aimed to determine whether there was a difference during the COVID-19 pandemic in the treated incidence of psychotic disorders and rates of admission to hospital for psychosis (including involuntary admission). Methods: Incident cases of first-episode psychosis in young people, aged 15 to 24, at an early intervention service in Melbourne from an 8-month period before the pandemic were compared with rates during the pandemic. Hospital admission rates for these periods were also compared. Results: Before the pandemic, the annual incidence of first-episode psychosis was 104.5 cases per 100,000 at-risk population, and during the pandemic it was 121.9 (incidence rate ratio = 1.14, 95% confidence interval = [0.92, 1.42], p = 0.24). Immediately after the implementation of restrictions, there was a non-significant reduction in the treated incidence (incidence rate ratio = 0.80, 95% confidence interval = [0.58, 1.09]), which was followed by a significant increase in the treated incidence in later months (incidence rate ratio = 1.94, 95% confidence interval = [1.52, 2.49]; incidence rate ratio = 1.64, 95% confidence interval = [1.25, 2.16]). Before the pandemic, 37.3% of young people with first-episode psychosis were admitted to hospital, compared to 61.7% during the pandemic (odds ratio = 2.71, 95% confidence interval = [1.73, 4.24]). Concerning the legal status of the admissions, before the pandemic, 27.3% were admitted involuntarily to hospital, compared to 42.5% during the pandemic (odds ratio = 1.97, 95% confidence interval = [1.23, 3.14]). Conclusion: There was a mild increase, which did not reach statistical significance, in the overall incidence of first-episode psychosis; however, the pattern of presentations changed significantly, with nearly twice as many cases presenting in the later months of the restrictions. There was a significant increase in both voluntary and involuntary admissions, and the possible explanations for these findings are discussed.