Browsing by Author "Jiang, Rong"
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Item Open Access A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.(PLoS One, 2013) Brummett, Beverly H; Babyak, Michael A; Jiang, Rong; Shah, Svati H; Becker, Richard C; Haynes, Carol; Chryst-Ladd, Megan; Craig, Damian M; Hauser, Elizabeth R; Siegler, Ilene C; Kuhn, Cynthia M; Singh, Abanish; Williams, Redford BPreviously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.Item Open Access A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.(PloS one, 2014-01) Brummett, Beverly H; Babyak, Michael A; Williams, Redford B; Harris, Kathleen Mullan; Jiang, Rong; Kraus, William E; Singh, Abanish; Costa, Paul T; Georgiades, Anastasia; Siegler, Ilene CPsychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.Item Open Access Accelerated epigenetic age as a biomarker of cardiovascular sensitivity to traffic-related air pollution.(Aging, 2020-12) Ward-Caviness, Cavin K; Russell, Armistead G; Weaver, Anne M; Slawsky, Erik; Dhingra, Radhika; Kwee, Lydia Coulter; Jiang, Rong; Neas, Lucas M; Diaz-Sanchez, David; Devlin, Robert B; Cascio, Wayne E; Olden, Kenneth; Hauser, Elizabeth R; Shah, Svati H; Kraus, William EBackground
Accelerated epigenetic age has been proposed as a biomarker of increased aging, which may indicate disruptions in cellular and organ system homeostasis and thus contribute to sensitivity to environmental exposures.Methods
Using 497 participants from the CATHGEN cohort, we evaluated whether accelerated epigenetic aging increases cardiovascular sensitivity to traffic-related air pollution (TRAP) exposure. We used residential proximity to major roadways and source apportioned air pollution models as measures of TRAP exposure, and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used Horvath epigenetic age acceleration (AAD) and phenotypic age acceleration (PhenoAAD) as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, and socioeconomic status.Results
We observed significant interactions between TRAP and both AAD and PhenoAAD. Interactions indicated that increased epigenetic age acceleration elevated associations between proximity to roadways and PAD. Interactions were also observed between AAD and gasoline and diesel source apportioned PM2.5.Conclusion
Epigenetic age acceleration may be a biomarker of sensitivity to air pollution, particularly for TRAP in urban cohorts. This presents a novel means by which to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.Item Open Access Determinants of Dropout from and Variation in Adherence to an Exercise Intervention: The STRRIDE Randomized Trials.(Translational journal of the American College of Sports Medicine, 2022-01) Collins, Katherine A; Huffman, Kim M; Wolever, Ruth Q; Smith, Patrick J; Siegler, Ilene C; Ross, Leanna M; Hauser, Elizabeth R; Jiang, Rong; Jakicic, John M; Costa, Paul T; Kraus, William EPurpose
This study aimed to characterize the timing and self-reported determinants of exercise dropout among sedentary adults with overweight or obesity. We also sought to explore variations in adherence among individuals who completed a 6- to 8-month structured exercise intervention.Methods
A total of 947 adults with dyslipidemia [STRRIDE I, STRRIDE AT/RT] or prediabetes [STRRIDE-PD] were enrolled to either control or to one of 10 exercise interventions, ranging from doses of 8-23 kcal/kg/week; intensities of 50%-75% V̇O2 peak; and durations of 6-8 months. Two groups included resistance training and one included dietary intervention (7% weight loss goal). Dropout was defined as an individual who withdrew from the study due a variety of determinants. Timing of intervention dropout was defined as the last session attended and categorized into phases. Exercise training adherence was calculated by dividing weekly minutes or total sets of exercise completed by weekly minutes or total sets of exercise prescribed. General linear models were used to characterize the associations between timing of dropout and determinant category.Results
Compared to exercise intervention completers (n=652), participants who dropped out (n=295) were on average non-white (98% vs. 80%, p<0.01), had higher body mass index (31.0 kg/m2 vs. 30.2 kg/m2; p<0.01), and were less fit at baseline (25.0 mg/kg/min vs. 26.7 ml/kg/min, p<0.01). Of those who dropped out, 67% did so prior to the start of or while ramping up to the prescribed exercise volume and intensity. The most commonly reported reason for dropout was lack of time (40%). Notably, among individuals who completed the ramp training period, subsequent exercise intervention adherence did not waiver over the ensuing 6-8 months of training.Conclusion
These findings are some of the first to delineate associations between the timing of dropout and dropout determinants, providing guidance to future exercise interventions to better support individuals at-risk for dropout.Item Open Access Effect of behavioral weight-loss program on biomarkers of cardiometabolic disease risk: Heart Health Study randomized trial.(Obesity (Silver Spring, Md.), 2023-02) Collins, Katherine A; Kraus, William E; Rogers, Renee J; Hauser, Elizabeth R; Lang, Wei; Jiang, Rong; Schelbert, Erik B; Huffman, Kim M; Jakicic, John MObjective
This study aimed to determine whether novel biomarkers of cardiometabolic health improve in response to a 12-month behavioral weight-loss intervention and to compare benefits of diet alone with diet plus physical activity for these biomarkers.Methods
Participants (N = 374) were randomized to either diet alone (DIET), diet plus 150 min/wk of prescribed moderate-intensity physical activity (DIET + PA150), or diet plus 250 min/wk of prescribed moderate-intensity physical activity (DIET + PA250). Biomarker concentrations were determined using nuclear magnetic resonance spectroscopy. Mixed models assessed for a time effect, group effect, or group by time interaction.Results
All groups significantly improved body weight (time: p < 0.0001), Lipoprotein Insulin Resistance Index score (time: p < 0.0001), Diabetes Risk Index score (time: p < 0.0001), branched-chain amino acid concentration (time: p < 0.0001), and GlycA concentration (time: p < 0.0001), with no group effect or group by time interactions.Conclusions
All intervention groups prompted a notable beneficial change among biomarkers of insulin resistance and cardiometabolic health. However, the addition of at least moderate-intensity physical activity to a diet-only intervention did not provide any additional benefit. These findings highlight that an average weight loss of approximately 10% profoundly impacts biomarkers of insulin resistance and cardiometabolic disease in adults with overweight or obesity.Item Open Access Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.(Genome medicine, 2021-04-30) Breeze, Charles E; Batorsky, Anna; Lee, Mi Kyeong; Szeto, Mindy D; Xu, Xiaoguang; McCartney, Daniel L; Jiang, Rong; Patki, Amit; Kramer, Holly J; Eales, James M; Raffield, Laura; Lange, Leslie; Lange, Ethan; Durda, Peter; Liu, Yongmei; Tracy, Russ P; Van Den Berg, David; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed MESA Multi-Omics Working Group; Evans, Kathryn L; Kraus, William E; Shah, Svati; Tiwari, Hermant K; Hou, Lifang; Whitsel, Eric A; Jiang, Xiao; Charchar, Fadi J; Baccarelli, Andrea A; Rich, Stephen S; Morris, Andrew P; Irvin, Marguerite R; Arnett, Donna K; Hauser, Elizabeth R; Rotter, Jerome I; Correa, Adolfo; Hayward, Caroline; Horvath, Steve; Marioni, Riccardo E; Tomaszewski, Maciej; Beck, Stephan; Berndt, Sonja I; London, Stephanie J; Mychaleckyj, Josyf C; Franceschini, NoraBackground
DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.Methods
The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses.Results
We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development.Conclusions
We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.Item Open Access Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants.(Translational psychiatry, 2020-10-20) Singh, Abanish; Babyak, Michael A; Sims, Mario; Musani, Solomon K; Brummett, Beverly H; Jiang, Rong; Kraus, William E; Shah, Svati H; Siegler, Ilene C; Hauser, Elizabeth R; Williams, Redford BIn prior work, we identified a novel gene-by-stress association of EBF1's common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to "racism/discrimination" (P = 0.036) and "not meeting basic needs" (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e-03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.Item Open Access Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene.(European journal of human genetics : EJHG, 2015-06) Singh, Abanish; Babyak, Michael A; Nolan, Daniel K; Brummett, Beverly H; Jiang, Rong; Siegler, Ilene C; Kraus, William E; Shah, Svati H; Williams, Redford B; Hauser, Elizabeth RWe performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps = 7.14E-09 to 2.33E-08, uncorrected; Ps = 1.99E-07 to 5.18E-07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps = 0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate = 0.26, P = 0.033, 95% CI = 0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate = 0.004, P = 0.34, 95% CI = -0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values = 0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease.Item Unknown Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.(European heart journal, 2021-03) Hartiala, Jaana A; Han, Yi; Jia, Qiong; Hilser, James R; Huang, Pin; Gukasyan, Janet; Schwartzman, William S; Cai, Zhiheng; Biswas, Subarna; Trégouët, David-Alexandre; Smith, Nicholas L; INVENT Consortium; CHARGE Consortium Hemostasis Working Group; GENIUS-CHD Consortium; Seldin, Marcus; Pan, Calvin; Mehrabian, Margarete; Lusis, Aldons J; Bazeley, Peter; Sun, Yan V; Liu, Chang; Quyyumi, Arshed A; Scholz, Markus; Thiery, Joachim; Delgado, Graciela E; Kleber, Marcus E; März, Winfried; Howe, Laurence J; Asselbergs, Folkert W; van Vugt, Marion; Vlachojannis, Georgios J; Patel, Riyaz S; Lyytikäinen, Leo-Pekka; Kähönen, Mika; Lehtimäki, Terho; Nieminen, Tuomo VM; Kuukasjärvi, Pekka; Laurikka, Jari O; Chang, Xuling; Heng, Chew-Kiat; Jiang, Rong; Kraus, William E; Hauser, Elizabeth R; Ferguson, Jane F; Reilly, Muredach P; Ito, Kaoru; Koyama, Satoshi; Kamatani, Yoichiro; Komuro, Issei; Biobank Japan; Stolze, Lindsey K; Romanoski, Casey E; Khan, Mohammad Daud; Turner, Adam W; Miller, Clint L; Aherrahrou, Redouane; Civelek, Mete; Ma, Lijiang; Björkegren, Johan LM; Kumar, S Ram; Tang, WH Wilson; Hazen, Stanley L; Allayee, HoomanAims
While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.Methods and results
We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.Conclusions
A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.Item Unknown Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease(Annals of Behavioral Medicine) Jiang, Rong; Collins, Katherine A; Huffman, Kim M; Hauser, Elizabeth R; Hubal, Monica J; Johnson, Johanna L; Williams, Redford B; Siegler, Ilene C; Kraus, William EAbstract Background Despite the benefits of exercise, many individuals are unable or unwilling to adopt an exercise intervention. Purpose The purpose of this analysis was to identify putative genetic variants associated with dropout from exercise training interventions among individuals in the STRRIDE trials. Methods We used a genome-wide association study approach to identify genetic variants in 603 participants initiating a supervised exercise intervention. Exercise intervention dropout occurred when a subject withdrew from further participation in the study or was otherwise lost to follow-up. Results Exercise intervention dropout was associated with a cluster of single-nucleotide polymorphisms with the top candidate being rs722069 (T/C, risk allele = C) (unadjusted p = 2.2 × 10−7, odds ratio = 2.23) contained within a linkage disequilibrium block on chromosome 16. In Genotype-Tissue Expression, rs722069 is an expression quantitative trait locus of the EARS2, COG7, and DCTN5 genes in skeletal muscle tissue. In subsets of the STRRIDE genetic cohort with available muscle gene expression (n = 37) and metabolic data (n = 82), at baseline the C allele was associated with lesser muscle expression of EARS2 (p < .002) and COG7 (p = .074) as well as lesser muscle concentrations of C2- and C3-acylcarnitines (p = .026). Conclusions Our observations imply that exercise intervention dropout is genetically moderated through alterations in gene expression and metabolic pathways in skeletal muscle. Individual genetic traits may allow the development of a biomarker-based approach for identifying individuals who may benefit from more intensive counseling and other interventions to optimize exercise intervention adoption. Clinical Trial information STRRIDE I = NCT00200993; STRRIDE AT/RT = NCT00275145; STRRIDE-PD = NCT00962962.Item Unknown Lack of Association of a Functional Polymorphism in the Serotonin Receptor Gene With Body Mass Index and Depressive Symptoms in a Large Meta-Analysis of Population Based Studies.(Frontiers in genetics, 2018-01) Brummett, Beverly H; Babyak, Michael A; Singh, Abanish; Hauser, Elizabeth R; Jiang, Rong; Huffman, Kim M; Kraus, William E; Shah, Svati H; Siegler, Ilene C; Williams, Redford BThe serotonin receptor 5-HTR2C is thought to be involved in the function of multiple brain structures. Consequently, the HTR2C gene has been studied extensively with respect to its association with a variety of phenotypes. One coding variant in the HTR2C gene, Cys23Ser (rs6318), has been associated with depressive symptoms. and adiposity; however, these findings have been inconsistent. The reasons for this mixed picture may be due to low statistical power or due to other factors such as failure to account for possible interacting environmental factors, such as psychosocial stress. Further, the literature around this polymorphism is marked by limited inclusion of persons of African ancestry. The present study sought to overcome these limitations and definitively determine the relationship of this polymorphism with depressive and obesity phenotypes in a large sample meta-analysis. Thus, we harmonized individual level data from 10 studies including the Women's Health Initiative, CARDIA, ARIC, Framingham Offspring, and the Jackson Heart Study, resulting in a sample of 27,161 individuals (10,457 Black women, 2,819 Black men, 7,419 White women, and 6,466 White men). We conducted a random effects meta-analysis using individual level data to examine whether the Cys23Ser variant-either directly, or conditionally depending on the level of psychosocial stress-was associated with depressive symptoms and body mass index (BMI). We found that psychosocial stress was associated with both depression and BMI, but that Cys23Ser was not directly associated with, nor did it modify the associations of psychosocial stress with depression or BMI. Thus, in the largest study of this polymorphism, we have determined that rs6318 is not associated with depression, or BMI.Item Unknown Malnutrition and Adverse Outcomes After Surgery for Head and Neck Cancer.(JAMA otolaryngology-- head & neck surgery, 2023-10) Reed, William T; Jiang, Rong; Ohnuma, Tetsu; Kahmke, Russel R; Pyati, Shreyas; Krishnamoorthy, Vijay; Raghunathan, Karthik; Osazuwa-Peters, NosayabaImportance
Patients with head and neck cancer (HNC) have an increased risk of malnutrition, partly due to disease location and treatment sequelae. Although malnutrition is associated with adverse outcomes, there is little data on the extent of outcomes and the sociodemographic factors associated with malnutrition in patients with HNC.Objectives
To investigate the association of race, ethnicity, and payer type with perioperative malnutrition in patients undergoing HNC surgery and how malnutrition affects clinical outcomes.Design, setting, and participants
This retrospective cohort study used data from the Premier Healthcare Database to assess adult patients who had undergone HNC surgery from January 2008 to June 2020 at 482 hospitals across the US. Diagnosis and procedure codes were used to identify a subset of patients with perioperative malnutrition. Patient characteristics, payer types, and hospital outcomes were then compared to find associations among race, ethnicity, payer type, malnutrition, and clinical outcomes using multivariable logistic regression models. Analyses were performed from August 2022 to January 2023.Exposure(s)
Race, ethnicity, and payer type for primary outcome, and perioperative malnutrition status, race, ethnicity, and payer type for secondary outcomes.Main outcome(s) and measure(s)
Perioperative malnutrition status. Secondary outcomes were discharge to home after surgery, hospital length of stay (LOS), total cost, and postoperative pulmonary complications (PPCs).Results
The study population comprised 13 895 adult patients who had undergone HNC surgery during the study period; they had a mean (SD) age of 63.4 (12.1) years; 9425 male (67.8%) patients; 968 Black (7.0%), 10 698 White (77.0%), and 2229 (16.0%) individuals of other races; and 887 Hispanic (6.4%) and 13 008 non-Hispanic (93.6%) individuals. Among the total sample, there were 3136 patients (22.6%) diagnosed with perioperative malnutrition. Compared with White patients and patients with private health insurance, the odds of malnutrition were higher for non-Hispanic Black patients (adjusted odds ratio [aOR], 1.31; 95% CI, 1.11-1.56), Medicaid-insured patients (aOR, 1.68; 95% CI, 1.46-1.95), and Medicare-insured patients (aOR, 1.24; 95% CI, 1.10-1.73). Black patients and patients insured by Medicaid had increased LOS, costs, and PPCs, and lower rates of discharge to home. Malnutrition was independently associated with increased LOS (β, 5.20 additional days; 95% CI, 4.83-5.64), higher costs (β, $15 722 more cost; 95% CI, $14 301-$17 143), increased odds of PPCs (aOR, 2.04; 95% CI, 1.83-2.23), and lower odds of discharge to home (aOR, 0.34; 95% CI, 0.31-0.38). No independent association between malnutrition and mortality was observed.Conclusions and relevance
This retrospective cohort study found that 1 in 5 patients undergoing HNC surgery were malnourished. Malnourishment disproportionately affected Black patients and patients with Medicaid, and contributed to longer hospital stays, higher costs, and more postoperative complications.Item Unknown Polymorphisms in the kinesin-like factor 1 B gene and risk of epithelial ovarian cancer in Eastern Chinese women.(Tumour Biol, 2015-09) Shi, Ting-Yan; Jiang, Zhi; Jiang, Rong; Yin, Sheng; Wang, Meng-Yun; Yu, Ke-Da; Shao, Zhi-Ming; Sun, Meng-Hong; Zang, Rongyu; Wei, QingyiThe kinesin-like factor 1 B (KIF1B) gene plays an important role in the process of apoptosis and the transformation and progression of malignant cells. Genetic variations in KIF1B may contribute to risk of epithelial ovarian cancer (EOC). In this study of 1,324 EOC patients and 1,386 cancer-free female controls, we investigated associations between two potentially functional single nucleotide polymorphisms in KIF1B and EOC risk by the conditional logistic regression analysis. General linear regression model was used to evaluate the correlation between the number of variant alleles and KIF1B mRNA expression levels. We found that the rs17401966 variant AG/GG genotypes were significantly associated with a decreased risk of EOC (adjusted odds ratio (OR) = 0.81, 95 % confidence interval (CI) = 0.68-0.97), compared with the AA genotype, but no associations were observed for rs1002076. Women who carried both rs17401966 AG/GG and rs1002076 AG/AA genotypes of KIF1B had a 0.82-fold decreased risk (adjusted 95 % CI = 0.69-0.97), compared with others. Additionally, there was no evidence of possible interactions between about-mentioned co-variants. Further genotype-phenotype correlation analysis indicated that the number of rs17401966 variant G allele was significantly associated with KIF1B mRNA expression levels (P for GLM = 0.003 and 0.001 in all and Chinese subjects, respectively), with GG carriers having the lowest level of KIF1B mRNA expression. Taken together, the rs17401966 polymorphism likely regulates KIF1B mRNA expression and thus may be associated with EOC risk in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.Item Unknown Survival Benefit of Germline BRCA Mutation is Associated with Residual Disease in Ovarian Cancer.(Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018-01) Shi, Tingyan; Wang, Pan; Tang, Wenbin; Jiang, Rong; Yin, Sheng; Shi, Di; Wang, Qing; Wei, Qingyi; Zang, RongyuBACKGROUND/AIMS:Prognostic value of germline BRCA1 or BRCA2 (gBRCA1/2) mutations in epithelial ovarian cancer (EOC) remains controversial, especially in the estimation of long-term survival. We previously reported the largest study of gBRCA1/2 mutation prevalence in Chinese EOC patients. The aim of this study is to further illustrate the correlation of residual disease and survival in BRCA-associated EOC in China. METHODS:In the current cohort consisting of 615 cases from the Chinese EOC genome-wide association study, we evaluated the association between gBRCA1/2 mutation and clinical outcomes. RESULTS:Overall, we did not find any significant difference between gBRCA1/2 mutation carriers and non-carriers in both progression-free survival (PFS) and overall survival (OS) (19.3 vs. 18.1 months and 77.2 vs. 73.2 months, P=0.528 and 0.147, HR 0.93 and 0.79, 95%CI 0.74-1.17 and 0.57-1.09, respectively). However, within three years after diagnosis, mutation carriers showed a longer OS than non-carriers (P=0.018, HR 0.53, 95%CI 0.31-0.90). Such a survival advantage decreased along with the extension of follow-up time. Quite interestingly, in the subgroup of patients with gross residual disease, mutation carriers had a longer survival than non-carriers (18.5 vs. 15.1 months and 68.5 vs. 54.3 months, P=0.046 and 0.038, HR 0.74 and 0.65, 95% CI 0.55-1.00 and 0.43-0.98, for PFS and OS respectively). CONCLUSIONS:Our findings provided the evidence that gBRCA1/2 mutation was not associated with survival in Chinese EOC patients, which possibly attributed to more than 37% of the patients without gross residual disease. Survival benefit of gBRCA1/2 mutation was prominent in ovarian cancer patients with gross residual disease.Item Unknown Systolic Blood Pressure and Socioeconomic Status in a large multi-study population.(SSM - population health, 2019-12) Brummett, Beverly H; Babyak, Michael A; Jiang, Rong; Huffman, Kim M; Kraus, William E; Singh, Abanish; Hauser, Elizabeth R; Siegler, Ilene C; Williams, Redford BThe present study used harmonized data from eight studies (N = 28,891) to examine the association between socioeconomic status (SES) and resting systolic blood pressure (SBP). The study replicates and extends our prior work on this topic by examining potential moderation of this association by race and gender. We also examined the extent to which body mass index (BMI), waist circumference (WC), and smoking might explain the association between SES and SBP. Data were available from six race/gender groups: 9200 Black women; 2337 Black men; 7248 White women; 6519 White men; 2950 Hispanic women; and 637 Hispanic men. Multivariable regression models showed that greater annual household income was associated with lower SBP in all groups except Hispanic men. The magnitude and form of this negative association differed across groups, with White women showing the strongest linear negative association. Among Black men and Hispanic women, the association was curvilinear: relatively flat among lower income levels, but then negative among higher income ranges. Education also was independently, negatively related to SBP, though evidence was weaker for race and gender differences in the strength of the association. Higher BMI and WC were associated with higher SBP, and current smoking with lower SBP. Inclusion of these risk factors resulted in only a modest change in the magnitude of the SBP and SES relation, accounting on average about 0.4 mmHg of the effect of income and 0.2 mmHg of the effect of education-effects unlikely to be clinically significant. Further understanding of mechanisms underlying the association between SBP and SES may improve risk stratification in clinical settings and potentially inform interventions aimed at reductions in social disparities in health.Item Unknown The association of accelerated epigenetic age with all-cause mortality in cardiac catheterization patients as mediated by vascular and cardiometabolic outcomes.(Clinical epigenetics, 2022-12) Jiang, Rong; Hauser, Elizabeth R; Kwee, Lydia Coulter; Shah, Svati H; Regan, Jessica A; Huebner, Janet L; Kraus, Virginia B; Kraus, William E; Ward-Caviness, Cavin KBackground
Epigenetic age is a DNA methylation-based biomarker of aging that is accurate across the lifespan and a range of cell types. The difference between epigenetic age and chronological age, termed age acceleration (AA), is a strong predictor of lifespan and healthspan. The predictive capabilities of AA for all-cause mortality have been evaluated in the general population; however, its utility is less well evaluated in those with chronic conditions. Additionally, the pathophysiologic pathways whereby AA predicts mortality are unclear. We hypothesized that AA predicts mortality in individuals with underlying cardiovascular disease; and the association between AA and mortality is mediated, in part, by vascular and cardiometabolic measures.Methods
We evaluated 562 participants in an urban, three-county area of central North Carolina from the CATHGEN cohort, all of whom received a cardiac catheterization procedure. We analyzed three AA biomarkers, Horvath epigenetic age acceleration (HAA), phenotypic age acceleration (PhenoAA), and Grim age acceleration (GrimAA), by Cox regression models, to assess whether AAs were associated with all-cause mortality. We also evaluated if these associations were mediated by vascular and cardiometabolic outcomes, including left ventricular ejection fraction (LVEF), blood cholesterol concentrations, angiopoietin-2 (ANG2) protein concentration, peripheral artery disease, coronary artery disease, diabetes, and hypertension. The total effect, direct effect, indirect effect, and percentage mediated were estimated using pathway mediation tests with a regression adjustment approach.Results
PhenoAA (HR = 1.05, P < 0.0001), GrimAA (HR = 1.10, P < 0.0001) and HAA (HR = 1.03, P = 0.01) were all associated with all-cause mortality. The association of mortality and PhenoAA was partially mediated by ANG2, a marker of vascular function (19.8%, P = 0.016), and by diabetes (8.2%, P = 0.043). The GrimAA-mortality association was mediated by ANG2 (12.3%, P = 0.014), and showed weaker evidence for mediation by LVEF (5.3%, P = 0.065).Conclusions
Epigenetic age acceleration remains strongly predictive of mortality even in individuals already burdened with cardiovascular disease. Mortality associations were mediated by ANG2, which regulates endothelial permeability and angiogenic functions, suggesting that specific vascular pathophysiology may link accelerated epigenetic aging with increased mortality risks.