Publications by authors named "Michael R Brown"

Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids.

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Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.

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Identification and mitigation of health barriers associated with social determinants of health (SDoH) is an increasingly recognized as an important component of healthcare provided by interprofessional teams. However, valid and reliable tools for assessing healthcare provider SDoH competency are lacking. This study describes the development of the University at Buffalo interprofessional SDoH scale (UB iSDoH scale) and examines its psychometric properties.

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Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.

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Background: Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample.

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  • * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
  • * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
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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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Purpose: The purpose of this study was to assess the knowledge, attitudes, and practices among providers and patients regarding hearing impairment and screening referrals in people with diabetes.

Methods: A cross-sectional survey design among health care providers and patients at an academic medical center in Oklahoma was used to gather knowledge, attitudes, and practices data.

Results: Only 25.

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Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.

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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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  • - The study investigates how the DASH diet score influences systolic blood pressure (BP) in relation to genetic factors, analyzing data from over 127,000 participants from different population groups, primarily European.
  • - Researchers identified several genetic loci associated with interactions between an individual's genetics and their response to the DASH diet, particularly focusing on the variant rs117878928 at chromosomal location 15q25.1.
  • - Results suggest significant gene-DASH diet interactions affecting systolic BP, highlighting the need for further research in larger, more diverse populations to confirm these findings.
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  • Educational attainment is linked to cardiovascular health, and a large genomic study examined how it interacts with cholesterol and triglyceride levels in nearly 226,315 individuals across five population groups.
  • The study identified 18 new genetic variations related to lipid levels—nine for low-density lipoprotein (LDL), seven for high-density lipoprotein (HDL), and two for triglycerides (TG)—some of which interact with educational attainment.
  • Researchers also found five gene targets that potentially interact with FDA-approved drugs, suggesting a connection between genetics and drug responses related to lipid metabolism and overall health.
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  • The study investigated how genetic variations (genotype) interact with dietary habits (specifically the DASH diet score) to influence systolic blood pressure (SBP).
  • Researchers analyzed a massive dataset of genetic information from over 127,000 individuals to identify specific genetic locations (loci) that may play a role in this interaction.
  • They found significant genetic interactions with the DASH diet score, especially at a specific gene location (rs117878928), indicating that diet can affect blood pressure differently based on an individual's genetic makeup, which highlights the need for further research with more diverse populations.
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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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  • Circulating metabolite levels can indicate health status, but the genetics behind them are not completely understood.
  • A study involving whole-genome sequencing analyzed data from 11,840 multi-ethnic participants and identified 1,985 new variant-metabolite associations, validating 761 known associations.
  • Further analysis showed links between metabolites and tissues, causal relationships with diseases, and potential regulation by plasma proteins, enhancing our understanding of the genetic factors in human metabolism and disease.
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Background: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total.

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  • A major study involving 580,869 participants identified 1,020 genetic signals linked to lung function impairment, which is crucial in understanding chronic obstructive pulmonary disease (COPD) and predicting mortality.
  • * The research found 559 genes related to lung function that were connected to 29 different biological pathways and demonstrated variations across ancestry, age, and smoking habits.
  • * Findings suggest potential new targets for therapy by highlighting specific genetic variants and proteins, ultimately contributing to better understanding and treatment of COPD.
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  • Fibrinogen is crucial for blood clotting and inflammation, and its circulating levels may be influenced by differences in DNA methylation at specific CpG sites.
  • An epigenome-wide association study analyzed blood DNA methylation and fibrinogen levels in over 18,000 diverse participants, revealing significant associations through advanced statistical models.
  • The study identified a total of 83 replicated CpG sites linked to fibrinogen, highlighting genes involved in inflammation, with many associations being affected but still significant after adjusting for C-reactive protein (CRP) levels.
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Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

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Though both genetic and lifestyle factors are known to influence cardiometabolic outcomes, less attention has been given to whether lifestyle exposures can alter the association between a genetic variant and these outcomes. The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium's Gene-Lifestyle Interactions Working Group has recently published investigations of genome-wide gene-environment interactions in large multi-ancestry meta-analyses with a focus on cigarette smoking and alcohol consumption as lifestyle factors and blood pressure and serum lipids as outcomes. Further description of the biological mechanisms underlying these statistical interactions would represent a significant advance in our understanding of gene-environment interactions, yet accessing and harmonizing individual-level genetic and 'omics data is challenging.

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The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci.

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