Publications by authors named "Kathleen A Ryan"

Article Synopsis
  • Antiplatelet therapy, particularly with P2Y receptor inhibitors alongside aspirin, is essential for treating coronary artery disease, and different medication options can help tailor patient care.
  • A study investigated the effects of a specific genetic mutation (G143E in CES1) on the effectiveness of clopidogrel and ticagrelor in inhibiting platelet aggregation in patients.
  • Results showed that the G143E mutation significantly affected platelet response to clopidogrel, but not to ticagrelor, indicating ticagrelor may provide more consistent treatment for patients with clopidogrel response-altering genetics.
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  • Researchers wanted to find out how where older adults live affects their recovery after a brain injury.
  • They looked at people over 65 who had brain injuries and divided them based on how disadvantaged their neighborhoods were.
  • The results showed that those living in less advantaged areas had fewer days at home after their injury, meaning their recovery was slower.
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  • Genetic studies have highlighted the need for more diverse research on plasma fibrinogen levels, as previous studies largely focused on Europeans, leading to gaps in understanding and missing heritability.
  • By analyzing data from whole-genome sequencing and genotype data from large cohorts, researchers identified 18 genetic loci related to fibrinogen levels, some of which are more common in African populations and include variants that may impact protein function.
  • The study's findings indicate a connection between fibrinogen levels and various health conditions, emphasizing the importance of whole-genome sequencing in discovering genetic factors in diverse populations and enhancing knowledge about fibrinogen regulation.
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  • Coronary artery calcification (CAC) is linked to heart disease and assessed through a genome-wide association study (GWAS) involving 22,400 participants from various backgrounds.
  • The study confirmed connections with four known genetic loci and discovered two new loci related to CAC, with supportive replication findings for both.
  • Functional tests suggest that ARSE promotes calcification in vascular smooth muscle cells and its variants may influence CAC levels, identifying ARSE as a key target for potential treatments in vascular calcific diseases.
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  • * Discovery of 7 new genetic loci associated with FVIII and 1 new locus for VWF, supporting their roles in thrombotic outcomes via Mendelian randomization.
  • * Functional testing revealed that silencing genes like B3GNT2 and CD36 impacted FVIII and VWF release from endothelial cells, indicating their potential regulatory roles.
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Introduction: Time spent at home may aid in understanding recovery following traumatic brain injury (TBI) among older adults, including those with Alzheimer's disease and related dementias (ADRD). We examined the impact of ADRD on recovery following TBI and determined whether socioeconomic disadvantages moderated the impact of ADRD.

Methods: We analyzed Medicare beneficiaries aged ≥65 years diagnosed with TBI in 2010-2018.

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  • A genome-wide association study was conducted on thyroid function, analyzing data from up to 271,040 European individuals, focusing on hormones like TSH, FT4, and T3.
  • The study identified 259 significant genetic associations for TSH (61% were novel), and notable findings for FT4 and T3, indicating that specific genes influence thyroid hormone levels and metabolism.
  • The research findings enhance the understanding of thyroid hormone roles and suggest that variations in thyroid function may impact various health conditions including cardiovascular issues, autoimmune diseases, and cancer.
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Common noncoding variants at the human 1p13.3 locus associated with SORT1 expression are among those most strongly associated with low-density lipoprotein cholesterol (LDL-C) in human genome-wide association studies. However, validation studies in mice and cell lines have produced variable results regarding the directionality of the effect of SORT1 on LDL-C.

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  • Nonalcoholic fatty liver disease (NAFLD) is widespread, partly genetic, and currently lacks effective treatment options.
  • A genome-wide association study (GWAS) identified several genetic variants linked to NAFLD, focusing on genes related to metabolism and liver function.
  • Genetic risk factors can help classify NAFLD into subtypes and significantly increase the risk of severe liver complications, potentially aiding in the development of targeted therapies.
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Background: Hip fracture is a disabling event experienced disproportionately by older adults with Alzheimer's disease or related dementias (ADRD). Claims information recorded prior to a hip fracture could provide valuable insights into recovery potential for these patients. Thus, our objective was to identify distinct trajectories of claims-based days at home (DAH) before a hip fracture among older adults with ADRD and evaluate associations with postfracture DAH and 1-year mortality.

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  • Genetic studies on plasma fibrinogen levels primarily focused on Europeans, revealing numerous associated regions, but there are gaps in understanding due to missing heritability and representation of non-Europeans.
  • The researchers utilized whole genome sequencing (WGS) and array-based genotyping data from large cohorts to identify 18 new genetic loci linked to fibrinogen levels, with some variants more common in African populations.
  • The study highlights the importance of WGS in discovering genetic variations across diverse populations, linking fibrinogen polygenic risk scores to increased risk for thrombotic and inflammatory diseases like gout.
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Objective: Postpregnancy weight retention contributes to obesity, but the long-term effect of parity on body mass index (BMI) and other cardiometabolic risk factors is unclear. We aimed to evaluate the relationship between parity and BMI among highly parous Amish women, both before and after menopause, and to evaluate the associations of parity with glucose, blood pressure, and lipids.

Methods: We conducted a cross-sectional study among 3,141 Amish women 18 years or older from Lancaster County, PA, who participated in our community-based Amish Research Program between 2003 and 2020.

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Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.

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  • The study investigates genetic variants linked to early-onset ischemic stroke (EOS) in individuals aged 18-59, contrasting with previous research focused on late-onset stroke (LOS).
  • Researchers conducted a meta-analysis involving 16,730 EOS cases and 599,237 controls to identify significant genetic associations and compared results between EOS and LOS.
  • Findings include two genetic variants associated with blood subgroups that show a stronger connection to EOS than LOS, indicating that genetic factors promoting blood clotting are particularly influential in early-onset cases.
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  • Common SNPs may account for 40-50% of human height variation, and this study identifies 12,111 SNPs linked to height from a large sample of 5.4 million individuals.
  • These SNPs cluster in 7,209 genomic segments, encompassing about 21% of the genome and showing varying densities enriched in relevant genes.
  • While these SNPs explain a substantial portion of height variance in European populations (40-45%), their predictive power is lower (10-24%) in other ancestries, suggesting a need for more research to enhance understanding in diverse populations.
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Thermogenic fat differentiation and function can be promoted through multiple pathways, resulting in a common cell phenotype characterized by the expression of Uncoupling Protein-1 and the ability to dissipate energy, but local and systemic stimuli are necessary to promote adequate thermogenic fat vascularization, which is a precondition for the transport of substrate and the dissipation of heat. Angiopoietin-2 is an important driver of vascularization, and its transcription is in part promoted by estrogen signaling. In this study we demonstrate that adipose tissue-specific knock out of Angiopoietin-2 causes a female-specific reduced thermogenic fat differentiation and function, resulting in obesity and impaired glucose tolerance with end-organ features consistent with metabolic syndrome.

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  • The QT interval is a key measure in electrocardiograms that indicates the timing of heart muscle contractions and recoveries; abnormalities can lead to serious heart conditions.
  • A study involving over 250,000 individuals identified many genetic loci linked to various heart rhythm measures, revealing important genetic factors associated with QT, JT, and QRS intervals.
  • The findings suggest that certain gene variations could inform new treatments for arrhythmias and highlight genetic pathways involved in heart function and energy metabolism.
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We screened 65 longitudinally collected nasal swab samples from 31 children aged 0-16 years who were positive for severe acute respiratory syndrome coronavirus 2 Omicron BA.1. By day 7 after onset of symptoms, 48% of children remained positive by rapid antigen test.

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Objectives: Few studies have addressed Black-White differences in left ventricular hypertrophy (LVH) in young stroke patients without a history of hypertension.

Methods: A case-only cross-sectional analysis performed in 2019 of data from the Stroke Prevention in Young Adults Study, a population-based case-control study of ischemic stroke patients ages 15-49. The main outcomes were hypertension indicators at the time of stroke hospitalization: self-reported history of hypertension, LVH by echocardiography (Echo-LVH) and LVH by electrocardiogram (ECG-LVH).

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Introduction In response to the coronavirus disease 2019 (COVID-19) pandemic, state and local governments implemented mitigation strategies, including lockdowns, thereby averting the typical fall/winter 2020 bronchiolitis season and reducing the incidence of respiratory viruses, such as respiratory syncytial virus (RSV). Florida implemented a strict lockdown from April 1, 2020, to April 30, 2020. The removal of lockdown precautions on September 25, 2020, was followed by an atypical out-of-season surge of bronchiolitis in April 2021.

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  • The study investigates the genetic factors contributing to the decline in estimated glomerular filtration rate (eGFR), a key indicator of kidney function, by analyzing data from 62 longitudinal studies involving over 343,000 participants.
  • Twelve significant genetic variants related to eGFR decline were identified, with most showing interaction effects based on age, which highlights how genetic influences on kidney function change as individuals get older.
  • The findings emphasize that individuals with certain genetic profiles face higher risks for kidney failure and acute kidney injury, providing valuable insights that could aid in drug development and strategies for managing kidney health.
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Article Synopsis
  • Reduced glomerular filtration rate (GFR) is a precursor to kidney failure, influenced by factors like genetics and diabetes (DM), but the interaction between these factors is not well understood.
  • A large-scale genome-wide association study (GWAS) analyzed eGFR across almost 1.5 million individuals, revealing distinct genetic loci that differ between those with and without diabetes.
  • The findings identified potential new targets for drug development aimed at protecting kidney function, highlighting that many drug interventions could be effective for both diabetic and non-diabetic populations.
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  • * The genome-wide association study (GWAS) identified 77 significant genetic loci linked to NAFLD, with 25 of these being newly discovered, demonstrating the complexity of its genetic basis across different ancestries.
  • * Further validation in other cohorts confirmed 17 specific single-nucleotide polymorphisms (SNPs) related to NAFLD, highlighting their relationships with metabolic and inflammatory traits, thus
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Background And Objectives: Stroke in young adults constitutes 15%-18% of all ischemic stroke cases. Black individuals have an excess risk of ischemic stroke especially in young adults. Although it is known that Black patients have a higher prevalence of hypertension and diabetes, few studies have addressed the association of concurrent multiple vascular risk factors with the excess risk of early-onset stroke among Black individuals.

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