Similar Patterns Of Association Research Articles

Feeding habits influence species habitat associations at the landscape scale in a diverse clade of Neotropical fishes

AbstractAimA primary goal of community ecology is to understand the mechanisms that drive species' spatial distribution and habitat associations. Species' geographic distribution can be influenced by the distribution of their prey partly because consumers' behaviour is oriented to optimal energy use during foraging. We analysed how differences in dietary preferences influence the spatial distribution and habitat associations of species at the landscape scale. We hypothesized that differences in feeding guilds will lead to divergent habitat association patterns among species.LocationAmazon River drainage basin.TaxonCharaciform fishes in the family Serrasalmidae (piranhas and pacus).MethodsWe used diet data to classify species into feeding guilds (frugivores, herbivores, piscivores, fin and scale feeders and planktivores). We used three proxies of habitat association derived from satellite products: floodplain extent, landscape heterogeneity and flood duration, in three distance buffers. We implemented phylogenetic generalized least squares models to evaluate the relationship between habitat association and feeding guilds.ResultsFrugivores, piscivores and fin and scale feeders presented similar patterns of habitat associations, with frugivores occupying wider areas of floodplain and greater landscape heterogeneity. Herbivores and planktivores were associated with smaller floodplain extents and lower landscape heterogeneity. All feeding guilds were associated with similar levels of flood duration.Main conclusionsDifferences in resource distribution (assessed through feeding guilds) can influence habitat association. Considering the hydrological variability (i.e. floodplain extent) and landscape heterogeneity that characterize floodplains, the patterns of habitat association vary with the spatial scale considered. This work highlights the importance of understanding species habitat associations by fish as well as food resource dynamics and floodplain dependence. This realization is critical for assessing the impact of anthropogenic activities on freshwater ecosystems.

Prenatal exposure to mixtures of phthalates and phenols and body mass index and blood pressure in Spanish preadolescents

BackgroundPregnant women are simultaneously exposed to several non-persistent endocrine-disrupting chemicals, which may influence the risk of childhood obesity and cardiovascular diseases later in life. Previous prospective studies have mostly examined single-chemical effects, with inconsistent findings. We assessed the association between prenatal exposure to phthalates and phenols, individually and as a mixture, and body mass index (BMI) and blood pressure (BP) in preadolescents. MethodsWe used data from the Spanish INMA birth cohort study (n = 1,015), where the 1st and 3rd- trimester maternal urinary concentrations of eight phthalate metabolites and six phenols were quantified. At 11 years of age, we calculated BMI z-scores and measured systolic and diastolic BP. We estimated individual chemical effects with linear mixed models and joint effects of the chemical mixture with hierarchical Bayesian kernel machine regression (BKMR). Analyses were stratified by sex and by puberty status. ResultsIn single-exposure models, benzophenone-3 (BP3) was nonmonotonically associated with higher BMI z-score (e.g. Quartile (Q) 3: β = 0.23 [95% CI = 0.03, 0.44] vs Q1) and higher diastolic BP (Q2: β = 1.27 [0.00, 2.53] mmHg vs Q1). Methyl paraben (MEPA) was associated with lower systolic BP (Q4: β = −1.67 [−3.31, −0.04] mmHg vs Q1). No consistent associations were observed for the other compounds. Results from the BKMR confirmed the single-exposure results and showed similar patterns of associations, with BP3 having the highest importance in the mixture models, especially among preadolescents who reached puberty status. No overall mixture effect was found, except for a tendency of higher BMI z-score and lower systolic BP in girls. ConclusionsPrenatal exposure to UV-filter BP3 may be associated with higher BMI and diastolic BP during preadolescence, but there is little evidence for an overall phthalate and phenol mixture effect.

Sociocultural drivers of body image and eating disorder risk in rural Nicaraguan women

ObjectiveTechnological and economic globalisation has been suggested as a cause of increasing rates of body dissatisfaction and eating disorders globally, especially as regards the impact of mass media on internalised body ideals. This process is rarely observed in action, however. The current work investigates multiple aspects of body ideals, body image, sociocultural attitudes and eating attitudes in 62 Creole and Mestizo women living in communities at differing stages of technological development on the Caribbean coast of NicaraguaMethod/resultsIn Study 1, women used 3D avatar software to create their own ‘ideal’ body without the constraints of ready-made stimuli. Analyses of resulting avatars showed that components of the ideal body shape (upper and lower body curvaceousness) but not body size (body mass) were associated with levels of film and television consumption. In Study 2, women completed measures of variables in the sociocultural model of eating disorder risk. As expected, body dissatisfaction mediated the relationship between internalisation of sociocultural body ideals and pathological eating attitudes. In contrast, body appreciation reduced pathological eating attitudes, via reduced body dissatisfaction. Finally, Study 3 measured sociocultural influences, body image and eating attitudes at 2 or 3 timepoints per woman; body dissatisfaction covaried with pathological eating attitudes across time. Ethnicity varied in its effects across studies.DiscussionTogether these data show that even at early stages of media acculturation, women may show similar patterns of association between sociocultural internalisation, body dissatisfaction and eating disorder risk as in high income nations. However, they also demonstrate unique aspects of this population’s body shape ideals, and the independent protective effect of body appreciation.

An Alcohol Symptom Checklist identifies high rates of alcohol use disorder in primary care patients who screen positive for depression and high-risk drinking

BackgroundAlthough alcohol use disorder can complicate depression management, there is no standard process for assessing AUD symptoms (i.e., AUD diagnostic criteria) in primary care for patients who screen positive for depression. This study characterizes the association between depressive symptoms and high-risk drinking reported by primary care patients on screening measures in routine care. Then, using data from a novel clinical program, this study characterizes the association between depressive symptoms and AUD symptoms reported by primary care patients with high-risk drinking via an Alcohol Symptom Checklist.MethodsIn this cross-sectional study, electronic health record data were obtained from patients who visited 33 Kaiser Permanente Washington primary care clinics between 03/2018 and 02/2020 and completed depression (PHQ-2) and alcohol consumption (AUDIT-C) screening measures as part of routine care (N = 369,943). Patients who reported high-risk drinking (AUDIT-C scores 7–12) also completed an Alcohol Symptom Checklist where they reported the presence or absence of 11 AUD criteria as defined by the DSM-5 (N = 8,184). Generalized linear models estimated and compared the prevalence of high-risk drinking (AUDIT-C scores 7–12) and probable AUD (2–11 AUD symptoms on Alcohol Symptom Checklists) for patients with and without positive depression screens.ResultsPatients who screened positive for depression had a 131% higher prevalence of high-risk drinking than those who screened negative (5.2% vs. 2.2%; p < 0.001). Among patients with high-risk drinking, positive depression screens were associated with a significantly higher prevalence of probable AUD (69.8% vs. 48.0%; p < 0.001), with large differences in the prevalence of probable AUD observed with increasing PHQ-2 scores (e.g., probable AUD prevalence of 37.6%, 55.3% and 65.2%, for PHQ-2 scores of 0, 1, and 2, respectively). Although the overall prevalence of high-risk drinking was higher for male patients, similar patterns of association between depression screens, high-risk drinking, and AUD symptoms were observed for male and female patients.ConclusionsPatients with positive depression screens are more likely to have high-risk drinking. Large percentages of patients with positive depression screens and high-risk drinking report symptoms consistent with AUD to healthcare providers when given the opportunity to do so using an Alcohol Symptom Checklist.

Patterns and predictors of elevated blood pressure and hypertension among primary school children in urban Kenya.

We examined the prevalence of elevated blood pressure (BP) and hypertension among 390 primary school children of different socioeconomic status (SES) in two urban settings in Kenya and explored the association between children's BP status and their sociodemographic characteristics, dietary behaviours and overweight/obesity status. Children's BP and anthropometric measurements were taken and parents, with the help of their children, completed questionnaires on the children's dietary behaviours. An average of three BP readings was used to calculate BP percentiles by age, sex and height. BMI-for-age z-scores, waist-circumference-to-height ratio and the sum of skinfold measures were calculated. We utilized prevalence ratio analysis to examine the association between BP and sociodemographic characteristics, dietary behaviours and overweight/obesity. About 9% of the school children had elevated BP and 33% had stage 1 hypertension. Among overweight children, the proportion of children with elevated BP was 1.85-fold greater and the proportion of children with hypertension was 1.83-fold greater compared with children with healthy body weight. Similar patterns of significant associations were seen among obese children, children with central obesity and children with high total skinfold values. The proportion of children with hypertension was 1.42-fold greater among children with high frequency of consumption of chips/crisps compared with children with lower frequency of consumption. These results increase our understanding BP patterns and determinants among school children in Kenya and can help inform noncommunicable disease prevention efforts.

Association of longitudinal changes in serum lipids with the natural history of subclinical hypothyroidism: A retrospective cohort study using data from the REACTION study.

SummaryBackgroundSubclinical hypothyroidism (SCH) often leads to alterations in lipid profile, which may negatively impact humans health. Whether lipids in turn affect the natural history of SCH is unknown. We aimed to assess the association between longitudinal changes in serum lipid levels and the natural history of SCH.MethodsThis retrospective cohort study using data from the REACTION study included 581 patients with SCH who were enrolled between July 1, 2011, and December 19, 2014, with a median follow-up of three [IQR, 2·86-3·21] years. Patients with missing data or conditions that can affect thyroid function were excluded. Changes in serum lipid levels were calculated from serum lipid measurements 3 years apart and classified in two ways: 1) the first, second, and third tertiles of the difference between baseline and follow-up and 2) the percent change from baseline, namely, serum lipid decrease ≥ 25%, minor change, and serum lipid increase ≥ 25%. The natural history of SCH includes regression to euthyroidism, SCH persistence, or progression to overt hypothyroidism (OH). Odds ratios (ORs) were estimated by multivariable logistic regression. Validation was performed on data from a health management cohort study conducted from January 1, 2012, to December 31, 2016, with a median follow-up of two [IQR, 1·92-2·08] years. After using the same inclusion and exclusion criteria as the REACTION cohort study, 412 patients with SCH were eligible for the validation analysis.FindingsThere were 132 (22·7%) men and 449 (77·3%) women in the study, with a median age of 56 [IQR,49-62] years. During follow-up, 270 (46·5%), 266 (45·8%), and 27 (4·6%) patients had regression to euthyroidism, persistent SCH, and progression to OH, respectively. Both grouping manners showed a significant association between changes in lipid levels and the natural history of SCH. A total cholesterol (TC)-level increase was independently associated with a greater risk of progression to OH (OR for ≥ 25% TC increase vs. minor change: 5·40; 95% CI 1·46-21·65), whereas TC-level declines increased the likelihood of regressing to euthyroidism (OR for ≥ 25% TC decrease vs. minor change: 3·45; 95% CI 1·09-12·43). Similarly, the likelihood of regression according to changes in triglyceride (TG) levels exhibited a consistent trend with that according to TC-level changes. A similar pattern of association was observed in the validation cohort.InterpretationChanges in serum lipid levels in SCH are associated with future progression or regression risk, suggesting that the changes in serum lipid levels may affect the natural history of SCH. Clinicians should pay attention to the long-term control of serum lipids levels in populations with SCH, which may benefit thyroid function.FundingThis work was supported by grants from the National Key Research and Development Program of China (2017YFC1309800), the National Natural Science Foundation (81430020, 82070818), and the “Outstanding University Driven by Talents” Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

Mining High-Level Imaging Genetic Associations via Clustering AD Candidate Variants with Similar Brain Association Patterns.

Brain imaging genetics examines associations between imaging quantitative traits (QTs) and genetic factors such as single nucleotide polymorphisms (SNPs) to provide important insights into the pathogenesis of Alzheimer’s disease (AD). The individual level SNP-QT signals are high dimensional and typically have small effect sizes, making them hard to be detected and replicated. To overcome this limitation, this work proposes a new approach that identifies high-level imaging genetic associations through applying multigraph clustering to the SNP-QT association maps. Given an SNP set and a brain QT set, the association between each SNP and each QT is evaluated using a linear regression model. Based on the resulting SNP-QT association map, five SNP–SNP similarity networks (or graphs) are created using five different scoring functions, respectively. Multigraph clustering is applied to these networks to identify SNP clusters with similar association patterns with all the brain QTs. After that, functional annotation is performed for each identified SNP cluster and its corresponding brain association pattern. We applied this pipeline to an AD imaging genetic study, which yielded promising results. For example, in an association study between 54 AD SNPs and 116 amyloid QTs, we identified two SNP clusters with one responsible for amyloid beta clearances and the other regulating amyloid beta formation. These high-level findings have the potential to provide valuable insights into relevant genetic pathways and brain circuits, which can help form new hypotheses for more detailed imaging and genetics studies in independent cohorts.

Parallel adaptation prompted core-periphery divergence of Ammopiptanthus mongolicus.

Range expansion requires peripheral populations to shift adaptive optima to breach range boundaries. Opportunities for range expansion can be assessed by investigating the associations of core-periphery environmental and genetic differences. This study investigates differences in the core-periphery adaptation of Ammopiptanthus mongolicus, a broad-leaved evergreen shrub species in a relatively homogeneous temperate Asian desert environment, to explore the environmental factors that limit the expansion of desert plants. Temperate deserts are characterized by severe drought, a large diurnal temperature range, and seasonality. Long-standing adaptation to the harsh desert environment may confine the genetic diversity of A. mongolicus, despite its distribution over a wide range of longitude, latitude, and altitude. Since range edges defined by climate niches may have different genetic responses to environmental extremes, we compared genome-wide polymorphisms between nine environmental core populations and ten fragmented peripheral populations to determine the “adaptive peripheral” populations. At least four adaptive peripheral populations had similar genetic-environmental association patterns. High elevations, summer drought, and winter cold were the three main determinants of converging these four adaptive peripheral populations. Elevation mainly caused similar local climates among different geographic regions. Altitudinal adaptation resulting from integrated environmental-genetic responses was a breakthrough in breaching niche boundaries. These peripheral populations are also located in relatively humid and warmer environments. Relaxation of the drought and cold constraints facilitated the genetic divergence of these peripheral populations from the core population’s adaptive legacy. We conclude that pleiotropic selection synchronized adaptative divergence to cold and drought vs. warm and humid environments between the core and peripheral populations. Such parallel adaptation of peripheral populations relies on selection under a background of abundant new variants derived from the core population’s standing genetic variation, i.e., integration of genetic surfing and local adaptation.

Vascular Risk Score and Associations With Past, Current, or Future Migraine in Women: Cohort Study.

Migraine has consistently been associated with an increased risk of cardiovascular disease (CVD) events. It remains, however, unclear to what extent cardiovascular risk profiles might be linked with migraine activity status and how these profiles relate to the development of migraine. We used data from a cohort study of female health professionals (Women's Health Study, n = 27,539, age ≥45 years at baseline) without a history of CVD or other major diseases and who provided a blood sample at baseline. Framingham risk scores (FRSs) estimating the 10-year risk of coronary heart disease calculated at baseline were used to create vascular risk categories. The presence or development of self-reported migraine was assessed by questionnaires. Women were classified as having no migraine, history of migraine (experienced migraine in the past but did not experience any migraine attacks in the year before enrollment), active migraine at baseline (active), or incident migraine (first report of migraine during follow-up but not at baseline). We used multinomial logistic regression models to calculate ORs for the association between FRS categories and migraine status. Of the 27,539 participants, a total of 21,927 women did not report migraine, 1,500 women reported a history of migraine, 3,579 had migraine at baseline, and 533 reported migraine for the first time during follow-up. The odds of the probability of having a history of migraine at baseline (vs never migraine) was 76% higher among those with FRS ≥10% compared with FRS ≤1% after adjustment (OR = 1.76, 95% CI 1.39-2.23). In contrast, having FRS ≥10% was associated with reduced odds of having active migraine at baseline (OR = 0.64, 95% CI 0.52-0.80) and with newly reported migraine during follow-up (OR = 0.42, 95% CI 0.22-0.81) when compared with women with FRS category ≤1% and those not reporting migraine. A similar association pattern was observed for FRS categories 5%-9% and 2%-4%. High FRS categories were only observed among women with a history of migraine but not with active migraine at baseline or incident migraine after baseline. Our results suggest that the life course of migraine should be considered when studying associations with the vascular system. Our data further suggest that a relatively healthy vascular system, as assessed by the FRS, is associated with active migraine status or developing migraine in the future.

Long-term air pollution exposure, greenspace and health-related quality of life in the ECRHS study

BackgroundAssociations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status. ObjectiveTo assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations. MethodsThe study was based on the participants in the second (2000–2002, n = 6542) and third (2011–2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO2, PM2.5 and PM10 annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status. ResultsThe mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO2, PM2.5 and PM10 concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were −0.69 [−1.23; −0.15], −1.79 [−2.88; −0.70], −1.80 [−2.98; −0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status. ConclusionEuropean adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations.

Two Kinesin-14A Motors Oligomerize to Drive Poleward Microtubule Convergence for Acentrosomal Spindle Morphogenesis in Arabidopsis thaliana.

Plant cells form acentrosomal spindles with microtubules (MTs) converged toward two structurally undefined poles by employing MT minus end-directed Kinesin-14 motors. To date, it is unclear whether the convergent bipolar MT array assumes unified poles in plant spindles, and if so, how such a goal is achieved. Among six classes of Kinesin-14 motors in Arabidopsis thaliana, the Kinesin-14A motors ATK1 (KatA) and ATK5 share the essential function in spindle morphogenesis. To understand how the two functionally redundant Kinesin-14A motors contributed to the spindle assembly, we had ATK1-GFP and ATK5-GFP fusion proteins expressed in their corresponding null mutants and found that they were functionally comparable to their native forms. Although ATK1 was a nuclear protein and ATK5 cytoplasmic prior to nuclear envelop breakdown, at later mitotic stages, the two motors shared similar localization patterns of uniform association with both spindle and phragmoplast MTs. We found that ATK1 and ATK5 were rapidly concentrated toward unified polar foci when cells were under hyperosmotic conditions. Concomitantly, spindle poles became perfectly focused as if there were centrosome-like MT-organizing centers where ATK1 and ATK5 were highly enriched and at which kinetochore fibers pointed. The separation of ATK1/ATK5-highlighted MTs from those of kinetochore fibers suggested that the motors translocated interpolar MTs. Our protein purification and live-cell imaging results showed that ATK1 and ATK5 are associated with each other in vivo. The stress-induced spindle pole convergence was also accompanied by poleward accumulation of the MT nucleator γ-tubulin. These results led to the conclusion that the two Kinesin-14A motors formed oligomeric motor complexes that drove MT translocation toward the spindle pole to establish acentrosomal spindles with convergent poles.

Circulating metabolites associated with incident myocardial infarction and stroke: A prospective cohort study of 90 438 participants.

The relevance between circulating metabolites and vascular events remains controversial and comprehensive studies are lacking. We sought to investigate the prospective associations of plasma metabolomics with risks of incident stroke, ischemic stroke (IS), hemorrhagic stroke (HS), and myocardial infarction (MI). Within the UK Biobank cohort, 249 circulating metabolites were measured in 90 438 participants without baseline vascular diseases. Cox proportional hazards regressions were applied to estimate adjusted hazard ratios (HRs) for per 1 standard deviation increment in metabolites. The least absolute shrinkage and selection operator algorithm was used for selecting metabolite subsets. During a median of 9.0 years of follow-up, we documented 833 incident stroke and 1256 MI cases. Lipid constituents, comprising cholesterol, cholesteryl esters, free cholesterol, phospholipids, and total lipids, in very low- (VLDL), intermediate- (IDL), and low-density lipoprotein (LDL) particles were positively associated with MI risk (HR=1.12 to 1.36; 95% CI=1.06 to 1.44), while in high-density lipoprotein (HDL) particles showed inverse associations (HR=0.68 to 0.81; 95% CI=0.63 to 0.87). Similar association pattern with MI was also observed for VLDL, IDL, LDL, and HDL particles themselves. In contrast, triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI risk (HR=1.14 to 1.28; 95% CI=1.08 to 1.35) and, to a slightly lesser extent, with stroke and IS. Unsaturation of fatty acids and albumin were inversely associated with risks of stroke, IS, and MI. In contrast, the linear association for HS is absent. When combining multiple metabolites, the metabolite risk score captured a drastically elevated risk of all vascular events, about twice that of any single metabolite. Taken together, circulating metabolites showed remarkably widespread associations with incident MI, but substantially weakened associations with risks of stroke and its subtypes. Exhaustive metabolomics profiling may shed light on vascular risk prediction and, in turn, guide pertinent strategies of intervention and treatment.

Abstract 2253: Plasma metabolomic profiles associated with early and late-stage high-grade serous ovarian cancer

Abstract Background: Ovarian cancer has poor survival due to more than 60% of patients being diagnosed at advanced stage. Therefore, discovery of novel, non-invasive early detection biomarkers has high potential to improve survival. Here, we identified plasma metabolomic profiles associated with early-stage and late-stage high-grade serous ovarian cancer (HGSOC), the most common histotype. Method: We examined 197 lipid and lipid-related metabolites measured using a validated, liquid chromatography tandem mass spectrometry method (Broad Institute, Cambridge, MA) in plasma collected prior to surgery from 40 early-stage and 40 late-stage HGSOC patients and 40 population-based controls matched on age, year, and menopausal status at blood draw. We used multivariable logistic regression, adjusted for matching factors, tubal ligation, oral contraceptive use, and parity, to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of ovarian cancer risk per 1 standard deviation increase in probit-transformed metabolite levels. We used Metabolite Set Enrichment Analysis (MSEA) to identify metabolite groups. We accounted for testing multiple correlated hypotheses using the number of effective tests (NEF) or false discovery rate (FDR). Results: Compared to controls, there were 34 metabolites associated with early-stage HGSOC and 88 metabolites associate with late-stage HGSOC (unadjusted p-value&amp;lt;0.05). All metabolites associated with risk of early-stage HGSOC and majority (n=80, 90%) of the metabolites associated with risk of late-stage HGSOC were inversely associated with ORs ranging from 0.28 to 0.48 for early-stage and 0.08 to 0.59 for late-stage HGSOC. Interestingly, the direction of association across all these metabolites were similar in both early-stage and late-stage HGSOC, with stronger effect estimates for late-stage HGSOC. After multiple testing correction, there were 9 statistically significant metabolites associated with risk of late-stage HGSOC (NEF p-value&amp;lt;0.05) whereas no individual metabolites remained associated with risk of early-stage HGSOC. MSEA revealed similar patterns of association compared to controls across the 11 lipid groups assessed in early and late-stage HGSOC cases. Metabolite groups of phosphatidylethanolamine plasmalogens and triglycerides were inversely associated with early-stage HGSOC compared to controls (FDR p-value&amp;lt;0.05). Metabolite groups of phosphatidylethanolamine plasmalogens and phosphatidylcholines were inversely, and diglycerides were positively associated with late-stage HGSOC compared to controls (FDR p-value&amp;lt;0.05). Conclusion: Our results revealed early-stage and late-stage HGSOC having similar plasma metabolomic profiles overall although there were more metabolites that were significantly associated with late-stage HGSOC than early-stage HGSOC compared to population-based controls. Citation Format: Naoko Sasamoto, Oana A. Zeleznik, Allison F. Vitonis, Daniel W. Cramer, Julian Avila-Pacheco, Clary B. Clish, Shelley S. Tworoger, Kathryn L. Terry. Plasma metabolomic profiles associated with early and late-stage high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2253.

Association between post-stroke psychological disorders, activity limitations and health-related quality of life in chronic stroke survivors in Benin

Purpose To evaluate the association between depression/anxiety and activity limitations and health-related quality of life (HRQoL) in chronic stroke survivors in Benin. Materials and methods One hundred and seventy-six chronic stroke survivors (113 males; mean age (±SD): 56.5 (±10.5) years old) were included. We used the Barthel index (BI) to assess activity limitations. Participants were screened for depression and anxiety symptoms using Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS). Euroqol-5 Dimensions-3 Levels (EQ-5D-3L) including a Visual Analog Scale (EQ-VAS) was used to assess HRQoL. Multivariate linear regressions were performed to determine the impact of psychological disorders on activity limitations and HRQoL. Results Depression (β=–0.54; p < 0.0001) and anxiety (β=–0.35; p < 0.0001) were negatively associated with activity limitations (R 2=0.60). Similar patterns of association were observed with HRQoL (β≤–0.28; p < 0.0001; R 2 ≥0.40). Inversely, occupational status showed positive association with EQ-5D-3L summary index scores (β = 0.21; p = 0.015). Conclusions Depression and anxiety had a negative impact on activity limitations and HRQoL in Beninese chronic stroke survivors. This call for action to integrate psychological interventions as part of rehabilitation programs in low and middle-income countries. Implications for rehabilitation Post-stroke depression and anxiety are quite common among stroke survivors in sub-Saharan Africa. Post-stroke depression and anxiety negatively impact activities and health-related quality of life in chronic stroke survivors in sub-Saharan Africa. Managing these post-stroke psychological disorders is necessary to promote the functional recovery and social reintegration of stroke survivors in their communities.

Longitudinal Changes in Cardiac Troponin and Risk of Heart Failure Among Black Adults

BackgroundAmong Black adults, high-sensitivity cardiac troponin I (hs-cTnI) is associated with heart failure (HF) risk. The association of longitudinal changes in hs-cTnI with risk of incident HF, HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), among Black adults is not well-established. Methods and ResultsThis study included Black participants from the Jackson Heart Study with available hs-cTnI data at visits 1 (2000–2004) and 2 (2005–2008) and no history of cardiovascular disease. Cox models were used to evaluate associations of categories of longitudinal change in hs-cTnI with incident HF risk. Among 2423 participants, 11.6% had incident elevation in hs-cTnI at visit 2, and 16.9% had stable or improved elevation (≤50% increase in hs-cTnI), and 4.0% had worsened hs-cTnI elevation (>50% increase). Over a median follow-up of 12.0 years, there were 139 incident HF hospitalizations (64 HFrEF, 58 HFpEF). Compared with participants without an elevated hs-cTnI, those with incident, stable or improved, or worsened hs-cTnI elevation had higher HF risk (adjusted hazard ratio 3.20 [95% confidence interval, 1.92–5.33]; adjusted hazard ratio 2.40, [95% confidence interval, 1.47–3.92]; and adjusted hazard ratio 8.10, [95% confidence interval, 4.74–13.83], respectively). Similar patterns of association were observed for risk of HFrEF and HFpEF. ConclusionsAmong Black adults, an increase in hs-cTnI levels on follow-up was associated with a higher HF risk. Lay SummaryThe present study included 2423 Black adults from the Jackson Heart Study with available biomarkers of cardiac injury and no history of cardiovascular disease at visits 1 and 2. The majority of participants did not have evidence of cardiac injury at both visits (67.5%), 11.6% had evidence of cardiac injury only on follow-up, 14.5% had stable elevations, 4.0% had worsened elevations, and 2.4% had improved elevations of cardiac injury biomarkers during follow-up. Compared with participants without evidence of cardiac injury, those with new, stable, and worsened levels of cardiac injury had a higher risk of developing heart failure. TweetAmong Black adults, persistent or worsening subclinical myocardial injury is associated with an elevated risk of HF.

Commercial outdoor plant nurseries as a confounder for electromagnetic fields and childhood leukemia risk.

BackgroundClose residential proximity to powerlines and high magnetic fields exposure may be associated with elevated childhood leukemia risks as reported by prior studies and pooled analyses. Magnetic fields exposure from high-voltage powerlines is associated with proximity to these powerlines and consequently with any factor varying with distance. Areas underneath powerlines in California may be sites for commercial plant nurseries that can use pesticides, a potential childhood leukemia risk factor. ObjectivesAssess if potential pesticide exposure from commercial plant nurseries is a confounder or interacts with proximity or magnetic fields exposure from high-voltage powerlines to increase childhood leukemia risk. MethodsA comprehensive childhood leukemia record-based case-control study with 5788 cases and 5788 controls (born and diagnosed in California, 1986–2008) was conducted. Pesticide, powerline, and magnetic field exposure assessment utilized models that incorporated geographical information systems, aerial satellite images, site visits and other historical information. ResultsThe relationship for calculated fields with childhood leukemia (odds ratio (OR) 1.51, 95% confidence interval (CI) 0.70–3.23) slightly attenuated when controlling for nursery proximity (OR 1.43, 95% CI 0.65–3.16) or restricting analysis to subjects living far (>300 m) from nurseries (OR 1.43, 95% CI 0.79–2.60). A similar association pattern was observed between distance to high-voltage powerlines and childhood leukemia. The association between nursery proximity and childhood leukemia was unchanged or only slightly attenuated when controlling for calculated fields or powerline distance; ORs remained above 2 when excluding subjects with high calculated fields or close powerline proximity (OR 2.16, 95% CI 0.82–5.67 and OR 2.15, 95% CI 0.82–5.64, respectively). The observed relationships were robust to different time periods, reference categories, and cut points. DiscussionClose residential proximity to nurseries is suggested as an independent childhood leukemia risk factor. Our results do not support plant nurseries as an explanation for observed childhood leukemia risks for powerline proximity and magnetic fields exposure, although small numbers of subjects concurrently exposed to high magnetic fields, close powerline proximity and plant nurseries limited our ability to fully assess potential confounding.

Predictors of Awareness of Functional Ability in People with Dementia: The Contribution of Personality, Cognition, and Neuropsychiatric Symptoms – Findings from the IDEAL Program

Introduction: Discrepancy scores reflecting the difference between parallel ratings made by people living with dementia (PwD) in the mild-to-moderate stages and by their informants provide a way to investigate awareness of functional ability in relation to activities of daily living (ADL). Methods: Two measures of ADL (Functional Activities Questionnaire; Dependence Scale) were completed by 1,227 PwD and their informants in the IDEAL cohort study baseline assessment. Self-rated and informant-rated scores were used to calculate discrepancies, which were used as an indicator of awareness of functional ability. Smaller discrepancy scores were considered to reflect greater awareness on the part of PwD. PwD completed questionnaires on depression, personality, comorbidities, neuropsychiatric symptoms, and completed a measure of cognition. Informants provided ratings of stress. Univariable and multiple regressions were used to investigate factors related to ADL discrepancy. Results: A similar pattern of associations were found for both ADL discrepancy scores. Smaller discrepancy scores were associated with higher levels of depression, higher neuroticism, fewer neuropsychiatric symptoms, higher comorbidity, lower carer stress, and receipt of less than 1 hour of care per day from the informant. Discussion/Conclusion: There was a clear pattern of factors that were associated with greater awareness for both measures of functional ability. These factors associated with smaller discrepancy scores could be used to identify PwD who might benefit from targeted interventions to support their independence.

Shared components of heritability across genetically correlated traits

Most disease-associated genetic variants are pleiotropic, affecting multiple genetically correlated traits. Their pleiotropic associations can be mechanistically informative: if many variants have similar patterns of association, they may act via similar pleiotropic mechanisms, forming a shared component of heritability. We developed pleiotropic decomposition regression (PDR) to identify shared components and their underlying genetic variants. We validated PDR on simulated data and identified limitations of existing methods in recovering the true components. We applied PDR to three clusters of five to six traits genetically correlated with coronary artery disease (CAD), asthma, and type II diabetes (T2D), producing biologically interpretable components. For CAD, PDR identified components related to BMI, hypertension, and cholesterol, and it clarified the relationship among these highly correlated risk factors. We assigned variants to components, calculated their posterior-mean effect sizes, and performed out-of-sample validation. Our posterior-mean effect sizes pool statistical power across traits and substantially boost the correlation (r2) between true and estimated effect sizes (compared with the original summary statistics) by 94% and 70% for asthma and T2D out of sample, respectively, and by a predicted 300% for CAD.

Gestational and childhood phthalate exposures and adolescent body composition: The HOME study

BackgroundEarly life phthalate exposures may disrupt metabolism but results from human studies are inconsistent and few have examined body composition during adolescence. We investigated associations of gestational and childhood urinary phthalate biomarker concentrations with body composition at age 12 years. MethodsWe used data from 206 mother-child pairs in a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003 to 2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed fat and lean mass of the whole body and android and gynoid subregions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores. Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. We assessed effect measure modification by child sex using stratified models. ResultsGenerally, urinary mono-benzyl phthalate (MBzP) concentrations were modestly associated with lower fat and lean mass. Each 10-fold increase in urinary MBzP concentrations during gestation and at ages 5 and 8 years was associated with a −0.34 (95%CI: −0.72, 0.05), −0.44 (95% CI: −0.83, −0.05), and −0.35 (95% CI: −0.71, 0.00) z-score difference in lean body mass index, respectively. Urinary monoethyl phthalate, mono-(3-carboxypropyl) phthalate, and summed di(2-ethylhexyl) phthalate metabolites were associated with greater lean mass at some exposure periods. Slightly weaker but similar patterns of association were found with other body composition measures; associations did not differ by child sex. ConclusionWhile most associations were weak, exposure to certain phthalates during gestation and childhood may be associated with adolescent body composition, particularly lean mass.

Methylation Subtypes of Primary Prostate Cancer Predict Poor Prognosis.

Patients with prostate cancer experience heterogeneous outcomes after radical prostatectomy. Genomic studies including The Cancer Genome Atlas (TCGA) have reported molecular signatures of prostate cancer, but few studies have assessed the prognostic effects of DNA methylation profiles. We conducted the largest methylome subtyping analysis for primary prostate tumors to date, using methylome data from three patient populations: TCGA, a prostate cancer cohort study conducted at the Fred Hutchinson Cancer Research Center (FH; Seattle, WA), and the Canadian International Cancer Genome Consortium (ICGC) cohort. Four subtypes were detected in the TCGA dataset, then independently assigned to FH and ICGC cohort data. The identified methylation subtypes were assessed for association with cancer prognosis in the above three patient populations. Using a set of hypermethylated CpG sites, four methylation subtypes were identified in TCGA. Compared with subtype 1, subtype 4 had an HR of 2.09 (P = 0.029) for biochemical recurrence (BCR) in TCGA patients. HRs of 2.76 (P = 0.002) for recurrence and 9.73 (P = 0.002) for metastatic-lethal (metastasis or prostate cancer-specific death) outcomes were observed in the FH cohort. A similar pattern of association was noted in the Canadian ICGC cohort, though HRs were not statistically significant. A hypermethylated subtype was associated with an increased hazard of recurrence and mortality in three studies with prostate tumor methylome data. Further molecular work is needed to understand the effect of methylation subtypes on cancer prognosis. This study identified a DNA methylation subtype that was associated with worse prostate cancer prognosis after radical prostatectomy.