Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs). METHOD: In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed. RESULTS: Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP. CONCLUSIONS: Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

CT of viral lower respiratory tract infections in adults: comparison among viral organisms and between viral and bacterial infections.

OBJECTIVE: We retrospectively compared the CT findings of consecutive viral and bacterial lower respiratory tract infections (LRTIs) to determine their imaging appearance and any definable differences among the causative viruses and between the viral and bacterial infections. MATERIALS AND METHODS: Imaging features of LRTI caused by influenza virus, respiratory syncytial virus (RSV), parainfluenza, adenovirus, and bacteria over a 33-month period were reviewed by three radiologists blinded to clinical and diagnostic information. Individual CT features and the dominant pattern of infection were recorded for each examination. Imaging characteristics were compared among the four respiratory viruses and between viral and bacterial infections. RESULTS: One hundred fifteen chest CT scans were analyzed (60 influenza virus, 19 RSV, 10 adenovirus, four parainfluenza virus, and 22 bacterial pneumonia LRTIs). Individual imaging findings and imaging patterns were seen in similar frequencies when we compared viral and bacterial LRTIs, with the exception of the diffuse airspace pattern, which was seen more frequently in bacterial infections. Although there was overlap in the imaging appearance of individual viruses, RSV and adenovirus tended to have characteristic imaging appearances. RSV presented with an airway-centric pattern of disease (13/19 cases [68%]) characterized by varying mixtures of tree-in-bud opacities and bronchial wall thickening, with or without peribronchiolar consolidation. Adenovirus typically appeared as multifocal consolidation or ground-glass opacity without airway inflammatory findings (7/10 cases [70%]). CONCLUSION: There is considerable overlap in the imaging appearance of viral and bacterial respiratory infections. However, some characteristic differences can be seen, especially with RSV and adenovirus infections.

Chest computed tomographic imaging characteristics of viral acute lower respiratory tract illnesses: a case-control study.

OBJECTIVE: This study aimed to determine whether computed tomographic (CT) findings can distinguish viral lower respiratory tract illness (LRTI) from other conditions. METHODS: Three radiologists reviewed CT images of patients with LRTI who underwent testing for respiratory viral infection. Imaging findings in subjects with positive viral assays were compared with subjects with negative assays. RESULTS: Of 334 subjects, 93 were positive for viral LRTI. Tree-in-bud opacities and bronchial wall thickening were observed more often in subjects with viral LRTI (P < 0.05). Multifocal airspace disease occurred with similar frequency in both groups. Diffuse airspace opacification was negatively associated with viral LRTI. Pleural effusion was observed more often among subjects without viral LRTI (P < 0.001). CONCLUSIONS: Airway inflammatory changes such as tree-in-bud opacities, bronchial wall thickening, and peribronchiolar consolidation are associated with community-acquired viral LRTI. Recognition of these findings should prompt testing for viral infection. Multifocal consolidation is commonly found in cases of viral LRTI but is nonspecific.