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Background: Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk.
Methods And Results: We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026).
Conclusion: Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069013 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099798 | PLOS |
Aging Clin Exp Res
December 2024
Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
Background: Malnutrition, post-stroke depression (PSD), post-stroke anxiety (PSA), and post-stroke fatigue (PSF) in stroke survivors have complex relationships and are associated with adverse stroke outcomes.
Aims: This research aims to explore the temporal and directional relationships between malnutrition, PSD, PSA, and PSF after stroke in older adults.
Methods: Patients aged 65 years and older with their first ischemic stroke from two centers were selected and assessed at baseline, 3 months and 12 months.
Ther Hypothermia Temp Manag
December 2024
Department of Cerebrovascular Diseases, Suining Central Hospital, Sichuan Province, China.
The application value of mechanical thrombectomy (MT) in acute large-vessel occlusion cerebral infarction has been confirmed, but considering the poor prognosis of large-core infarction (LCI), the current guidelines and practices are based on anterior circulation small-core infarction. Reducing the perioperative complications of thrombectomy in LCIs is the key to saving more patients previously considered unsuitable for thrombectomy. Patients with acute anterior circulation cerebral infarction who were admitted to Suining Central Hospital of Sichuan Province from January 2022 to December 2023 and whose Alberta Stroke Program Early Computed Tomography Score value was 3-5 (the score range was 0-10, and the lower the score was, the larger the infarct area) or whose infarct core volume was ≥70 mL and who received MT were enrolled consecutively.
View Article and Find Full Text PDFA previously developed algorithm for the preliminary identification of protein proteoforms associated with post-translational modifications (PTMs) based on 2D electrophoresis data (DOI: 10.18097/BMCRM00191) has been used in this study for analysis of experimental data obtained using mice and reported in two papers by different authors. The authors of the first paper identified 8 groups of spots on 2D electrophoretic maps corresponding to 8 proteins with at least two unconcretised proteoforms.
View Article and Find Full Text PDFFront Oncol
December 2024
Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Prostate cancer is a common malignancy with an increasing incidence in ageing populations. However, older patients with prostate cancer are often underrepresented in traditional clinical trials. The electronic Prostate Cancer Australian and Asian Database (ePAD) is a multi-centre, multi-national prospective clinical registry, that records real world data from a broader population.
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January 2025
Neurology and Neurosurgery Department Hospital Moinhos de Vento, Porto Alegre, RS, Brazil.
Background: Current literature highlights a gap in precise stroke cost data for Latin America. This study measures the real costs associated with acute ischemic stroke care in Latin America using Time-Driven Activity-Based Costing (TDABC). The findings aim to lay a solid foundation for adopting value-based healthcare (VBHC) strategies in the region.
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