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Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics, and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads, and prioritize genes for functional follow-up studies.

Background The public health emergency of coronavirus disease (COVID-19) is rapidly evolving worldwide; some countries, including Spain, have implemented restrictive measures. Populations that are vulnerable to this outbreak and its physical and mental health effects include community-dwelling older adults with mild cognitive impairment or mild dementia. Telehealth is a potential tool to deliver health care and decrease exposure risk. Objective The aims of this study were to explore the impact of confinement on the health and well-being of community-dwelling older adults with mild cognitive impairment or mild dementia, to provide television-based and telephone-based health and social support, and to study the effects of a television-based assistive integrated technology, TV-AssistDem (TeleVision-based ASSistive Integrated Service to supporT European adults living with mild DEMentia or mild cognitive impairment). Methods A telephone-based survey was administered in Spain to 93 participants in the TV-AssistDem clinical trial from March 25 to April 6, 2020. Results Of the respondents, 60/93 (65%) were women. The mean age was 73.34 (SD 6.07), and 69/93 (74%) lived accompanied. Lockdown measures forced 17/93 respondents (18%) to change their living arrangements. Health status was found to be optimal in 89/93 respondents (96%), with no COVID-19 symptoms. Grocery and pharmacy outings were performed by family members of 68/93 participants (73%); 57 (61%) reported overall well-being, and 65 (70%) maintained their sleep quality. However, participants living alone reported greater negative feelings and more sleeping problems. Regarding leisure activities, 53/93 respondents (57%) took walks, 32 (35%) played memory games, 55 (60%) watched television, and 91 (98%) telephoned relatives. 58/93 (64%) respondents reported accessing moderate or too much COVID-19 information, 89 (97%) received it from television, and 56 (62%) stated that their understanding of the information was extreme. 39/93 (39%) respondents had contacted health and social services, while 29 (31%) requested information regarding these services during the telephone call. There were no significant differences in health and well-being between the intervention and control groups. Respondents with TV-AssistDem performed more memory exercises (24/93, 52% vs 8/93, 17.4%; P<.001) than control respondents. Conclusions Our findings suggest that during COVID-19 confinement, the physical and mental health and well-being was optimal for the majority of our vulnerable population. However, those living alone reported greater negative psychological effects and sleeping problems. Measures adopted to address the negative experiences of confinement included keeping informed about the situation, accessing health and social services, having a support network that prevents risk of exposure to COVID-19 and guarantees food and medical supplies, a daily routine with maintained sleeping habits and leisure activities, staying physically and mentally active with cognitive stimulation exercises, and ensuring social connectedness using technology. Television sets were preferred technological devices to access COVID-19 information, watch television as a recreational activity, and perform memory exercises as an intellectual activity. Television-based telehealth support using TV-AssistDem demonstrated potential for cognitive stimulation. Trial Registration ClinicalTrials.gov NCT03653234; https://clinicaltrials.gov/ct2/show/NCT03653234