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deCODE Genetics (Iceland)
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2021 · Nature Genetics · 1,622 citations
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder 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 expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
2019 · 50 citations
Oceanography and Marine Biology
Coastal plankton show fluctuations in abundance and species composition. Resting stage (cyst) production is a common strategy adopted by hundreds of plankton species to ensure reproduction and to avoid adverse conditions. During the resting period, these species are normally absent from the water column, and cysts produced in the plankton accumulate in the sediment where they wait for the return of suitable conditions. A portion of the cyst bank does not hatch, instead undergoing a dormancy that may extend for decades. Confined coastal areas accumulate cysts in sediment due to one or more possibilities, including reduced water movement/hydrodynamics, high population density, abundance of cyst-producing species, and the absence or scarcity of possible cyst consumers in the benthos. The pelagic-benthic nexus, which affects both the sediment and the water column (and possibly sea ice) is still poorly understood. In fact, the presence of cysts in the life cycle of organisms is likely to have considerable consequences for the ecology of coastal plankton, as well as the evolution and biogeography of species. This review aims to depict the presence (and even abundance) of resting stages in marine environments and their impact on ecosystem functioning. The review starts with a description of encysted resting stages in all marine planktonic taxa, listing a total of 501 species with known cysts, and methods and tools for their collection and study. The physiology and timing of the rest period is then described for various taxa, followed by a discussion of the evolutionary implications of resting. The presence of encysted stages in different realms and phyla of plankton suggests an ancient origin and a successive diversification of morphologies that, today, roughly characterise each taxa. Ecological and biogeographical implications stem from this general framework and support the hypothesis of seasonal occurrences of planktonic life in ecosystems where productivity is suspended for a long time (e.g. in polar seas). The potential to suspend or resume life has implications for human activities, such as the risk of translocations through ship ballast water and contamination of water and seafood with toxins but also the benefit of cysts for the production of aquaculture feed. The review concludes with perspectives on present knowledge and outstanding questions to address in future studies.