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Nature Papers on Factors Influencing SARS-CoV-2 Pathogenesis, Bipolar Disorder GWAS

By analyzing SARS-CoV-2 RNA sequencing data, a team led by scientists from the University of Lyon and the University of Miami identify a series of host and viral factors that appear to affect pathogenesis. As they report in Communications Biology, the investigators analyzed differential gene expression in human lung cells infected by SARS-CoV-2 or other respiratory viruses to identify gene-, isoform-, and pathway-level responses that specifically characterize SARS-CoV-2 infection. They then used a bioinformatics approach to predict interactions between the SARS-CoV-2 RNA genome and human proteins that may be involved in viral replication, transcription, or translation. They find differential expression of a number of known immunoregulatory genes as well as upregulation of immunoregulatory transposable element families in SARS-CoV-2-infected cells. The team also identified a viral sequence variant that is significantly associated with COVID-19 patient age. The findings, the study's authors write, could help inform the development of prophylactic and therapeutic treatments for SARS-CoV-2 infection.

A genome-wide association study of more than 40,000 people with bipolar disorder is published in Nature Genetics this week, providing new insights into the underlying biology of this heritable mental illness. An international team including investigators from Mount Sinai performed the GWAS of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, identifying 64 associated genomic loci. Other findings include disease risk alleles enriched in genes in synaptic signaling pathways and brain-expressed genes, as well as significant signal enrichment in genes encoding targets of drugs including antipsychotics, antiepileptics, and anesthetics. The scientists also found 15 genes strongly linked to bipolar disorder via gene expression and encoding druggable targets. The results "advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads, and prioritize genes for functional follow-up studies," they write. GenomeWeb has more on this, here.