Publications by authors named "W Craig Johnson"

4,715 Publications

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Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights into Cardiovascular Disease.

Circulation 2021 Nov 24. Epub 2021 Nov 24.

Department of Exercise Science, University of South Carolina, Columbia, SC.

Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Proteomic profiling of 1,301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥ 5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study. We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8 × 10. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β = 0.61±0.05, p-value = 3.27 × 10) and MMP-3 (β = -0.60±0.05, p = 1.67 × 10), as well as a completely novel pleiotropic locus at the gene, associated with nine proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1 associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β = 0.34±0.04, p = 1.34 × 10) as well as an association between ATTR amyloidosis and RBP4 levels in community dwelling individuals without heart failure. Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation and myocardial function.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055117DOI Listing
November 2021

Characterization of polycyclic aromatic hydrocarbons in the Great Lakes Basin using dreissenid mussels.

Environ Monit Assess 2021 Nov 20;193(12):833. Epub 2021 Nov 20.

National Ocean Service, National Oceanic and Atmospheric Administration, National Centers for Coastal Ocean Science, 1305 East West Highway, Silver Spring, N/SCI1MD, 20910, USA.

The National Oceanic and Atmospheric Administration (NOAA), National Centers for Coastal Ocean Science (NCCOS) Mussel Watch Program (MWP), conducts basin-wide monitoring and place-based assessments using dreissenid mussels as bioindicators of chemical contamination in the Laurentian Great Lakes. Polycyclic aromatic hydrocarbons (PAHs) body burden results for the period 2009-2018 were combined into one dataset from multiple MWP studies allowing for a robust characterization of PAH contamination. Patterns in PAH data were identified using descriptive statistics and machine learning techniques. Relationships between total PAH concentration in dreissenid mussel tissue, impervious surface percentages, and PAH relative concentration were identified and used to build a predictive model for the Great Lakes Basin. Significant positive correlation was identified by the Spearman's rank correlation test between total PAH concentration and percent impervious surface. The findings support the paradigm that PAHs are primarily derived from land-based sources. Offshore and riverine locations had the lowest and highest median total PAH concentrations, respectively. PAH assemblages and ratios indicated that pyrogenic sources were more predominant than petrogenic sources and that PAHs at offshore sites exhibited relatively more weathering compared to inshore sites.
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http://dx.doi.org/10.1007/s10661-021-09401-7DOI Listing
November 2021

Take 10: A Resident Well-Being Initiative and Burnout Mitigation Strategy.

J Surg Educ 2021 Oct 27. Epub 2021 Oct 27.

Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

Objective: Physician training is associated with stressors which contribute to burnout. Individual and institutional level strategies can be employed to address resident burnout; however, time is an often-reported barrier in initiating recommended well-being activities. We hypothesize that brief bursts of well-being activities that are conducive to a resident schedule can mitigate burnout.

Design: This is a prospective observational study following burnout after implementation of an institution-wide, well-being initiative called "Take 10."

Setting: In the present study, the "Take 10" initiative, meditating or exercising for a minimum of 10 minutes per day 3 times a week, was encouraged at Vanderbilt University Medical Center, a tertiary care center in Nashville, Tennessee.

Participants: Following implementation of the initiative, 254 residents from surgical, procedural, and non-procedural specialties were invited to complete surveys assessing compliance with encouraged "Take 10" activities as well as rates of burnout over a 5-month period. A total of 201 surveys were completed during the study period.

Results: Overall, burnout rates were worse for females (Odds Ratio [OR] = 3.7 | Confidence Interval [CI] = 1.57, 9.05), better for those living with others (OR = 0.22 | CI = 0.07, 0.64), and better for those participating in "Take 10" initiatives (OR = 0.71 | CI = 0.58, 0.86). There was a significant difference in resident-reported burnout (Control = 85.3% vs Intervention = 58.2% | p < 0.01) and Resident Well-Being Index score (Control = 3.73 vs Intervention=2.93 | p < 0.01), when "Take 10" initiatives were employed.

Conclusions: "Take 10" is a low cost and low intensity initiative for individuals and programs to use to mitigate burnout.
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http://dx.doi.org/10.1016/j.jsurg.2021.09.022DOI Listing
October 2021

Primary stroke prevention worldwide: translating evidence into action.

Lancet Public Health 2021 Oct 28. Epub 2021 Oct 28.

Institute for Health Metrics Evaluation, University of Washington, Seattle, WA, USA; National Institute for Stroke and Applied Neurosciences, School of Clinical Sciences, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand; Scientific and Educational Department, Research Centre of Neurology, Moscow, Russia. Electronic address:

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.
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http://dx.doi.org/10.1016/S2468-2667(21)00230-9DOI Listing
October 2021

A Genome-Phenome Association study in native microbiomes identifies a mechanism for cytosine modification in DNA and RNA.

Elife 2021 Nov 8;10. Epub 2021 Nov 8.

Research department, New England Biolabs Inc, Ipswich, United States.

Shotgun metagenomic sequencing is a powerful approach to study microbiomes in an unbiased manner and of increasing relevance for identifying novel enzymatic functions. However, the potential of metagenomics to relate from microbiome composition to function has thus far been underutilized. Here, we introduce the Metagenomics Genome-Phenome Association (MetaGPA) study framework, which allows linking genetic information in metagenomes with a dedicated functional phenotype. We applied MetaGPA to identify enzymes associated with cytosine modifications in environmental samples. From the 2365 genes that met our significance criteria, we confirm known pathways for cytosine modifications and proposed novel cytosine-modifying mechanisms. Specifically, we characterized and identified a novel nucleic acid modifying enzyme, 5-hydroxymethylcytosine carbamoyltransferase, that catalyzes the formation of a previously unknown cytosine modification, 5-carbamoyloxymethylcytosine, in DNA and RNA. Our work introduces MetaGPA as a novel and versatile tool for advancing functional metagenomics.
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http://dx.doi.org/10.7554/eLife.70021DOI Listing
November 2021
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