Prosocial behavior during adolescence has been associated with better physical health, including slower epigenetic aging. However, little is known about the specific role of empathy in epigenetic aging and the mechanisms explaining this relationship. One such mechanism may be substance use, which is predicted by low empathy and contributes to accelerated epigenetic aging.
View Article and Find Full Text PDFNeurobiol Pain
October 2024
This study aimed to determine the nature of the relationship between the internalized stigma of chronic pain (ISCP), the pace of biological aging, and racial disparities in nonspecific chronic low back pain (CLBP). We used Dunedin Pace of Aging from the Epigenome (DunedinPACE), Horvath's, Hannum's, and PhenoAge clocks to determine the pace of biological aging in adults, ages 18 to 82 years: 74 no pain, 56 low-impact pain, and 76 high-impact pain. Individuals with high-impact pain reported higher levels of ISCP and DunedinPACE compared to those with low-impact or no pain (p < 0.
View Article and Find Full Text PDFImportance: The clinical utility of polygenic risk scores (PRS) for blood pressure (BP) response to antihypertensive treatment (AHT) has not been elucidated.
Objective: To investigate the ability of a systolic BP (SBP) PRS to predict AHT response and apparent treatment-resistant hypertension (aTRH).
Design, Setting, And Participants: The Genetics of Hypertension Associated Treatments (GenHAT) study was an ancillary pharmacogenomic study to the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
Earlier pubertal timing is associated with accelerated epigenetic aging, but the underlying mechanisms are not well understood. This three-wave longitudinal study examined negative health behaviors, specifically substance use, short sleep duration, and poor diet quality in middle adolescence, as mediators of links between earlier phenotypic and perceived pubertal timing measured in early adolescence and epigenetic aging on three epigenetic clocks in late adolescence (GrimAge, DunedinPACE, and PhenoAge). Phenotypic pubertal timing measured physical pubertal maturation relative to chronological age, whereas perceived pubertal timing was based on adolescents' subjective interpretation of their pubertal timing relative to their peers.
View Article and Find Full Text PDFThe Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) is a hybrid of the Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets, and its association with renal outcomes remains unclear. In the REasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort, diet data were collected at baseline using food frequency questionnaires. Modified Poisson regression was used to examine the association of MIND diet with incident chronic kidney disease (CKD).
View Article and Find Full Text PDFKey Points: The predictive performance of an African ancestry–specific polygenic risk score (PRS) was comparable to a European ancestry–derived PRS for kidney traits. However, multi-ancestry PRSs outperform single-ancestry PRSs in Black American populations. Predictive accuracy of PRSs for CKD was improved with the use of race-free eGFR.
View Article and Find Full Text PDFType 2 diabetes (T2D) is caused by both genetic and environmental factors and is associated with an increased risk of cardiorenal complications and mortality. Though disproportionately affected by the condition, African Americans (AA) are largely underrepresented in genetic studies of T2D, and few estimates of heritability have been calculated in this race group. Using genome-wide association study (GWAS) data paired with phenotypic data from ~ 19,300 AA participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, Genetics of Hypertension Associated Treatments (GenHAT) study, and the Electronic Medical Records and Genomics (eMERGE) network, we estimated narrow-sense heritability using two methods: Linkage-Disequilibrium Adjusted Kinships (LDAK) and Genome-Wide Complex Trait Analysis (GCTA).
View Article and Find Full Text PDFKawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines.
View Article and Find Full Text PDFMosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.
View Article and Find Full Text PDFApart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS) across four cohorts of European (N=491,111) and African (N=21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R differences among strata.
View Article and Find Full Text PDFMediation analysis is an increasingly popular statistical method for explaining causal pathways to inform intervention. While methods have increased, there is still a dearth of robust mediation methods for count outcomes with excess zeroes. Current mediation methods addressing this issue are computationally intensive, biased, or challenging to interpret.
View Article and Find Full Text PDFMany oncology drugs have been found to induce cardiotoxicity in a subset of patients, which significantly limits their clinical use and impedes the benefit of lifesaving anticancer treatments. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carry donor-specific genetic information and have been proposed for exploring the interindividual difference in oncology drug-induced cardiotoxicity. Herein, we evaluated the inter- and intraindividual variability of iPSC-CM-related assays and presented a proof of concept to prospectively predict doxorubicin (DOX)-induced cardiotoxicity (DIC) using donor-specific iPSC-CMs.
View Article and Find Full Text PDFAfrican Americans (AAs) have been underrepresented in polygenic risk score (PRS) studies. Here, we integrated genome-wide data from multiple observational studies on type 2 diabetes (T2D), encompassing a total of 101,987 AAs, to train and optimize an AA-focused T2D PRS (PRSAA), using a Bayesian polygenic modeling method. We further tested the score in three independent studies with a total of 7,275 AAs and compared the PRSAA with other published scores.
View Article and Find Full Text PDFIntroduction: Kawasaki disease (KD) is a diffuse vasculitis in children. Response to high dose intravenous gamma globulin (IVIG), the primary treatment, varies according to genetic background. We sought to identify genetic loci, which associate with treatment response using whole genome sequencing (WGS).
View Article and Find Full Text PDFBackground: Spontaneous intracerebral hemorrhage (ICH) is associated with a high case fatality rate in resource-limited settings. The independent predictors of poor outcome after ICH in sub-Saharan Africa remains to be characterized in large epidemiological studies. We aimed to determine factors associated with 30-day fatality among West African patients with ICH.
View Article and Find Full Text PDFIntroduction: Non-cigarette tobacco (NCT) represents a form of tobacco use with a misperceived significance in chronic disease events. Whether NCT use is sufficient to promote stroke events, especially among Africans, is yet to be understood. This study assessed the relationship between NCT use and stroke among indigenous Africans.
View Article and Find Full Text PDFAssociations of HLA class II alleles with genital chlamydial infection outcomes have been reported, especially . However, the potential role of in influencing reinfection risk has still not been established. The purpose of this study was to determine whether the association of with chlamydia reinfection was impacted by any other nearby HLA class II variants that were also associated with reinfection.
View Article and Find Full Text PDFThis study aimed to determine if and how the pace of biological aging was associated with nonspecific chronic low back pain (cLBP) and compare what measure of epigenetic age acceleration most strongly predicts cLBP outcomes. We used the Dunedin Pace of Aging from the Epigenome (DunedinPACE), Horvath's, Hannum's, and PhenoAge clocks to determine the pace of biological aging in 69 cLBP, and 49 pain-free controls (PFCs) adults, ages 18 to 85 years. On average, participants with cLBP had higher DunedinPACE (P < .
View Article and Find Full Text PDFChronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years.
View Article and Find Full Text PDF