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Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of abdominal aortic aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in 10 cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects [Partners Biobank cohort 1 (PBIO)] as replication. Maximum anterior-posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In genome-wide association study (GWAS) on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = -0.02, SE = 0.004, P-value = 2.10 × 10-8). The association replicated in the PBIO1 cohort (P-value = 8.19 × 10-4). In exome-array single-variant analysis (P-value threshold = 9 × 10-7), the lowest P-value was found for rs239259 located in SLC22A20 (beta = 0.007, P-value = 1.2 × 10-5). In the gene-based analysis (P-value threshold = 1.85 × 10-6), PCSK5 showed an association with AAD (P-value = 8.03 × 10-7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = -0.003, P-value = 0.02), triglycerides (beta = -0.16, P-value = 0.008) and height (beta = 0.03, P-value < 0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Exoma/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , TriglicerídeosRESUMO
Short empirically-supported scales or individual items are preferred in comprehensive surveys, brief screeners, and experience sampling studies. To that end, we examined the Short Almost Perfect Scale (SAPS) to evaluate empirical support for the interchangeability of items to measure perfectionistic strivings (Standards) and perfectionistic concerns (Discrepancy). Based on a large and diverse sample (N = 1,103) and tests of tau-equivalence (equal factor loadings) for each respective set of items, Study 1 advanced a subset of SAPS items to measure Standards (2 items) and Discrepancy (3 items). Cross-sectional gender and race/ethnicity invariance were supported, and in structural equations analyses, the SAPS5 factors were significantly associated with depression, state anxiety, life satisfaction, and gratitude. Study 2 cross-validated Study 1 measurement and structural findings with a new U.S. sample (N = 803). The three items representing the Discrepancy (perfectionistic concerns) factor also were supported in a cross-national comparison between the U.S. sample and a scale development sample in New Zealand (N = 3,921). For the most part, across both studies and all analyses, the three Discrepancy items were empirically interchangeable indicators of perfectionistic concerns and comparably strong predictors of psychological outcomes, supporting their use in studies or other contexts with space or time restrictions for measurement.
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The current study explored the intelligibility and acceptability ratings of dysarthric speakers with African American English (AAE) and General American English (GAE) dialects by listeners who identify as GAE or AAE speakers, as well as listener ability to identify dialect in dysarthric speech. Eighty-six listeners rated the intelligibility and acceptability of sentences extracted from a passage read by speakers with dysarthria. Samples were used from the Atlanta Motor Speech Disorders Corpus and ratings were collected via self-report. The listeners identified speaker dialect in a forced-choice format. Listeners self-reported their dialect and exposure to AAE. AAE dialect was accurately identified in 63.43% of the the opportunities; GAE dialect was accurately identified in 70.35% of the opportunities. Listeners identifying as AAE speakers rated GAE speech as more acceptable, whereas, listeners identifying as GAE speakers rated AAE speech as more acceptable. Neither group of listeners demonstrated a difference in intelligibility ratings. Exposure to AAE had no effect on intelligibility or acceptability ratings. Listeners can identify dialect (AAE and GAE) with a better than chance degree of accuracy. One's dialect may have an effect on intelligibility and acceptability ratings. Exposure to a dialect did not affect listener ratings of intelligibility or acceptability.
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BACKGROUND: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variations to the QT interval in the population. METHODS: We performed a genome-wide association study of the QTc in 84 630 UK Biobank participants and created a polygenic risk score (PRS). Among 26 976 participants with whole-genome sequencing and ECG data in the TOPMed (Trans-Omics for Precision Medicine) program, we identified 160 carriers of putative pathogenic rare variants in 10 genes known to be associated with the QT interval. We examined QTc associations with the PRS and with rare variants in TOPMed. RESULTS: Fifty-four independent loci were identified by genome-wide association study in the UK Biobank. Twenty-one loci were novel, of which 12 were replicated in TOPMed. The PRS composed of 1 110 494 common variants was significantly associated with the QTc in TOPMed (ΔQTc/decile of PRS=1.4 ms [95% CI, 1.3 to 1.5]; P=1.1×10-196). Carriers of putative pathogenic rare variants had longer QTc than noncarriers (ΔQTc=10.9 ms [95% CI, 7.4 to 14.4]). Of individuals with QTc>480 ms, 23.7% carried either a monogenic rare variant or had a PRS in the top decile (3.4% monogenic, 21% top decile of PRS). CONCLUSIONS: QTc duration in the population is influenced by both rare variants in genes underlying cardiac repolarization and polygenic risk, with a sizeable contribution from polygenic risk. Comprehensive assessment of the genetic determinants of QTc prolongation includes incorporation of both polygenic and monogenic risk.
Assuntos
Estudo de Associação Genômica Ampla , Síndrome do QT Longo , Eletrocardiografia , Heterozigoto , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Herança Multifatorial , Sequenciamento Completo do GenomaRESUMO
Meta-analysis of associations between rare outcomes and binary exposures are particularly important in studies of a drug's potential side-effects. But meta-analysis of the resulting 2 × 2 $$ 2\times 2 $$ contingency tables presents substantial practical difficulties, as analysts are currently forced to pick between "exact" inference-that eliminates concern over using large-sample approximations with small cell counts-and explicitly allowing for heterogeneity of the underlying effects. A controversial example is given by the Avandia meta-analysis (Nissen and Wolski. N Engl J Med. 2007;356(24):2457-2471) of rosiglitazone's effects on myocardial infarction and death. While the initial Avandia analysis-using simple methods-found a significant effect, its results conflict with subsequent re-analyses that use either exact methods, or that explicitly acknowledge the plausible heterogeneity. In this article, we aim to resolve these difficulties, by providing an exact (albeit conservative) method that is valid under heterogeneity. We also provide a measure of the degree of conservatism, that indicates the approximate extent of the excess coverage. Applied to the Avandia data, we find support for Nissen and Wolski 2007's original results. Given that our method does not require strong assumptions or large cell counts, and provides intervals around the well-known conditional maximum likelihood estimate, we anticipate that it could be an attractive default method for meta-analysis of 2 × 2 $$ 2\times 2 $$ tables featuring rare events.
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Infarto do Miocárdio , Humanos , Rosiglitazona/uso terapêutico , Funções VerossimilhançaRESUMO
A body of research has been dedicated to demonstrating the relationship of perfectionism with a range of mental health indicators. Self-critical perfectionism, a component of perfectionism, has been framed primarily in a negative light within the mental health context. Given that research informs educational and clinical practices, it is important to explore the degree to which such findings generalize across cultures and subcultures. The current meta-analytic research systemically collated studies conducted with Asian college students with a particular attention to exploring whether orientation to Asian culture and cultural values correspondingly moderates the relationship between self-critical perfectionism and depressive symptoms. The degree of upholding Asian cultural values was represented by group identity (i.e., Asian American and Asian international). Eleven studies (N = 3,239) were identified through the literature search. Findings from the random-effects meta-analysis indicated a significant relationship between self-critical perfectionism and depressive symptoms in the overall sample. The group identity significantly moderated the relationship; among Asian international college students, self-critical perfectionism appeared to have a less harmful effect on mental distress compared to Asian American college students. Self-cultivation-one of the salient and virtuous Asian cultural values that aligns with self-critical perfectionism-may have motivated continuous striving for self-improvement to fulfill the honorable duty for their family for Asian international students. Additional findings and implications of the study are further discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Asiático , Perfeccionismo , Humanos , Depressão/psicologia , Estudantes/psicologia , EscolaridadeRESUMO
BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. RESULTS: Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7). CONCLUSIONS: Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.
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Estudo de Associação Genômica Ampla , Medicina de Precisão , Pressão Sanguínea/genética , Ligação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do GenomaRESUMO
With advances in whole-genome sequencing (WGS) technology, more advanced statistical methods for testing genetic association with rare variants are being developed. Methods in which variants are grouped for analysis are also known as variant-set, gene-based, and aggregate unit tests. The burden test and sequence kernel association test (SKAT) are two widely used variant-set tests, which were originally developed for samples of unrelated individuals and later have been extended to family data with known pedigree structures. However, computationally efficient and powerful variant-set tests are needed to make analyses tractable in large-scale WGS studies with complex study samples. In this paper, we propose the variant-set mixed model association tests (SMMAT) for continuous and binary traits using the generalized linear mixed model framework. These tests can be applied to large-scale WGS studies involving samples with population structure and relatedness, such as in the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine (TOPMed) program. SMMATs share the same null model for different variant sets, and a virtue of this null model, which includes covariates only, is that it needs to be fit only once for all tests in each genome-wide analysis. Simulation studies show that all the proposed SMMATs correctly control type I error rates for both continuous and binary traits in the presence of population structure and relatedness. We also illustrate our tests in a real data example of analysis of plasma fibrinogen levels in the TOPMed program (n = 23,763), using the Analysis Commons, a cloud-based computing platform.
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Estudos de Associação Genética , Modelos Genéticos , Sequenciamento Completo do Genoma , Cromossomos Humanos Par 4/genética , Computação em Nuvem , Feminino , Fibrinogênio/análise , Fibrinogênio/genética , Genética Populacional , Humanos , Masculino , National Heart, Lung, and Blood Institute (U.S.) , Medicina de Precisão , Projetos de Pesquisa , Fatores de Tempo , Estados UnidosRESUMO
Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint < 5 × 10-8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint < 5 × 10-8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint = 2 × 10-6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint < 10-3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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Estudo de Associação Genômica Ampla , Hipertensão , Pressão Sanguínea/genética , Loci Gênicos/genética , Humanos , Hipertensão/genética , Polimorfismo de Nucleotídeo Único/genética , Sono/genéticaRESUMO
[Figure: see text].
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Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/imunologia , Espessura Intima-Media Carotídea , Receptores de Lipopolissacarídeos/análise , Monócitos/imunologia , Receptores de IgG/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Doenças das Artérias Carótidas/etnologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI/análise , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Research is needed to understand the effects that perfectionism may have in the occupational sector and whether its implications vary cross-nationally. In the current study the relationship of perfectionism on workaholism and work engagement was assessed through multiple groups structural equations models to compare strengths of association in the two countries after measurement invariance was examined for the measures in a sample of 804 U.S. and Italian participants. Evidence of similarities but also some differences were found between the countries. In particular, perfectionistic strivings was similarly related to workaholism in both the countries, whereas it was more strongly related to work engagement in Italy than in U.S. A statistically significant difference for work engagement (Italians more engaged that Americans) was also found, whereas no differences were found for workaholism. Cross-sectional nature of the study and culture used as a proxy is the main limitations. However, the cross-cultural approach adopted in the current study allowed us to report that evidence provided in a country might not be directly applied to another country, even if cultures are quite similar.
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Perfeccionismo , Estudos Transversais , Humanos , ItáliaRESUMO
Growing incidence of nonsuicidal self-injury (NSSI) and a lack of intensive examination of NSSI variability among adolescents justify identification of latent classes based on the endorsement of different NSSI behaviors. Latent class analysis was used to detect the heterogeneity of past month NSSI among 322 high school students (73.2% female). Two interpretable latent classes emerged. The Severe/Multimethod NSSI class (39%) engaged in almost all forms of NSSI with high intensity and motivated mainly for intrapersonal reasons. The results imply that compared to Mild/Moderate NSSI group (61%), the Severe class is at greater risk for poor mental health, which can exacerbate further NSSI acts. In school settings, identifying adolescents who are vulnerable for more severe NSSI can help to interrupt NSSI trajectories to emerging adulthood.
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Comportamento Autodestrutivo , Adolescente , Adulto , Feminino , Humanos , Análise de Classes Latentes , Masculino , Comportamento Autodestrutivo/psicologia , Estudantes/psicologiaRESUMO
The purpose of this study was to test if coronavirus disease 2019 (COVID-19) traumatic stress predicts posttraumatic stress disorder (PTSD) symptoms after cumulative trauma and whether there is a three-way interaction between COVID-19 traumatic stress, cumulative trauma, and race in the prediction of PTSD. Using a cross-sectional design, a diverse sample of 745 participants completed measures of cumulative trauma, COVID-19 traumatic stress, and PTSD. COVID-19 traumatic stress accounted for a significant amount of the variance in PTSD above and beyond cumulative trauma. A significant interaction effect was found, indicating that the effect of COVID-19 traumatic stress in predicting PTSD varied as a function of cumulative trauma and that the effects of that interaction were different for Asians and Whites. There were generally comparable associations between COVID-19 traumatic stress and PTSD at low and high levels of cumulative trauma across most racial groups. However, for Asians, higher levels of cumulative trauma did not worsen the PTSD outcome as a function of COVID Traumatic Stress but did at low levels of cumulative trauma.
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COVID-19 , Transtornos de Estresse Pós-Traumáticos , Estudos Transversais , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , População BrancaRESUMO
BACKGROUND: The Inventory of Statements About Self-Injury (ISAS) is a psychometrically valid tool to evaluate the motives of nonsuicidal self-injury (NSSI), but there are a few studies that test gender differences in the factor structure of the measurement. However, several differences across gender were identified in NSSI (e.g., in prevalence, methods, functions). Therefore, our study focused on further analyses of the dimensionality of the ISAS functions. METHODS: Among Hungarian adolescents with a history of NSSI (N = 418; 70.6% girls; mean age was 16.86, SD = 1.45), confirmatory factor analysis and exploratory structural equation modeling frameworks were used to test the factor structure of the ISAS part II. RESULTS: Results support the two-factor structure of the questionnaire. Intrapersonal and interpersonal motivation factors emerged in the whole sample, but this factor structure varied across gender. Among girls, intrapersonal motivation of NSSI was associated with higher loneliness, more inflexible emotion regulation, and a more pronounced level of internalizing and externalizing mental illness symptoms. CONCLUSIONS: Our findings provide sufficiently solid arguments for the need to examine NSSI functionality separately for adolescent girls and boys because there were clear gender differences in the motives underlying NSSI. In addition, precise scanning of patterns of NSSI functions may further help us to identify the most at-risk adolescents regarding self-injury.
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Comportamento Autodestrutivo , Adolescente , Análise Fatorial , Feminino , Humanos , Hungria , Masculino , Psicometria , Comportamento Autodestrutivo/diagnóstico , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Religious/spiritual (R/S) growth is a core domain of posttraumatic growth (PTG). However, research on R/S growth following disasters has over-relied on retrospective self-reports of growth. We therefore examined longitudinal change in religiousness/spirituality following two disasters. METHOD: Religious survivors of Hurricanes Harvey (Study 1) and Irma (Study 2) completed measures of perceived R/S PTG, general religiousness/spirituality ("current standing"-R/S PTG), and subfacets of religiousness/spirituality (spiritual fortitude, religious motivations, and benevolent theodicies). In Study 1, 451 participants responded at 1-month and 2-month postdisaster. In Study 2, participants responded within 5-days predisaster and at 1-month (N = 1,144) and 6-months postdisaster (N = 684). RESULTS: In both studies, perceived R/S PTG was weakly related to longitudinal increases in general religiousness/spirituality and in most of its subfacets, but reliable growth in any R/S outcome was rare. Additionally, Study 2 revealed evidence that actual change in psychological well-being is associated with actual (but not perceived) R/S PTG, but disaster survivors tend to exhibit declines in their religiousness/spirituality, spiritual fortitude, and religious motivations. CONCLUSIONS: Results suggest disaster survivors are only modestly accurate in perceiving how much positive R/S change they experience following a disaster. We discuss implications for clinical practice, scientific research, and empirical and conceptual work on PTG more broadly.
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Desastres , Crescimento Psicológico Pós-Traumático , Adaptação Psicológica , Humanos , Estudos Retrospectivos , Espiritualidade , SobreviventesRESUMO
When testing genotype-phenotype associations using linear regression, departure of the trait distribution from normality can impact both Type I error rate control and statistical power, with worse consequences for rarer variants. Because genotypes are expected to have small effects (if any) investigators now routinely use a two-stage method, in which they first regress the trait on covariates, obtain residuals, rank-normalize them, and then use the rank-normalized residuals in association analysis with the genotypes. Potential confounding signals are assumed to be removed at the first stage, so in practice, no further adjustment is done in the second stage. Here, we show that this widely used approach can lead to tests with undesirable statistical properties, due to both combination of a mis-specified mean-variance relationship and remaining covariate associations between the rank-normalized residuals and genotypes. We demonstrate these properties theoretically, and also in applications to genome-wide and whole-genome sequencing association studies. We further propose and evaluate an alternative fully adjusted two-stage approach that adjusts for covariates both when residuals are obtained and in the subsequent association test. This method can reduce excess Type I errors and improve statistical power.
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Estudos de Associação Genética , Modelos Genéticos , Simulação por Computador , Estudo de Associação Genômica Ampla , Genótipo , Hemoglobinas/metabolismo , Hispânico ou Latino , Humanos , Modelos Lineares , FenótipoRESUMO
Background and Purpose- Serum cholesterol variability, independent of mean, has been associated with stroke, white matter hyperintensities on cranial magnetic resonance imaging (MRI), and other cardiovascular events. We sought to assess the relationship between total serum cholesterol (TC) variability and cranial MRI findings of subclinical or covert vascular brain injury in a longitudinal, population-based cohort study of older adults. Methods- In the Cardiovascular Health Study, we assessed associations between intraindividual TC mean, trend, and variability over ≈5 years with covert brain infarction (CBI) and white matter grade (WMG) on cranial MRI. Mean TC was calculated for each study participant from 4 annual TC measurements between 2 MRI scans. TC trend was calculated as the slope of the linear regression of the TC measurements, and TC variability was calculated as the SD of the residuals from the linear regression. We evaluated the association of intraindividual TC variability with incident CBI and worsening WMG between 2 MRI scans in primary analyses and with prevalent CBI number and WMG on the follow-up MRI scan in secondary analyses. Results- Among participants who were eligible for the study and free of clinical stroke before the follow-up MRI, 17.9% of 1098 had incident CBI, and 27.8% of 1351 had worsening WMG on the follow-up MRI. Mean, trend, and variability of TC were not associated with these outcomes. TC variability, independent of mean and trend, was significantly associated with the number of CBI (ß=0.009 [95% CI, 0.003-0.016] P=0.004; N=1604) and was associated with WMG (ß, 0.009 [95% CI, -0.0002 to 0.019] P=0.055; N=1602) on the follow-up MRI. Conclusions- Among older adults, TC variability was not associated with incident CBI or worsening WMG but was associated with the number of prevalent CBI on cranial MRI. More work is needed to validate and to clarify the mechanisms underlying such associations.
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Infarto Encefálico/patologia , Traumatismo Cerebrovascular/sangue , Colesterol/sangue , Acidente Vascular Cerebral/patologia , Idoso , Encéfalo/patologia , Infarto Encefálico/sangue , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Crânio/patologia , Acidente Vascular Cerebral/sangueRESUMO
SUMMARY: The Genomic Data Storage (GDS) format provides efficient storage and retrieval of genotypes measured by microarrays and sequencing. We developed GENESIS to perform various single- and aggregate-variant association tests using genotype data stored in GDS format. GENESIS implements highly flexible mixed models, allowing for different link functions, multiple variance components and phenotypic heteroskedasticity. GENESIS integrates cohesively with other R/Bioconductor packages to build a complete genomic analysis workflow entirely within the R environment. AVAILABILITY AND IMPLEMENTATION: https://bioconductor.org/packages/GENESIS; vignettes included. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Genômica , Software , Testes Genéticos , Genoma , Análise de SequênciaRESUMO
BACKGROUND: Cox proportional hazards regression models are used to evaluate associations between exposures of interest and time-to-event outcomes in observational data. When exposures are measured on only a sample of participants, as they are in a case-cohort design, the sampling weights must be incorporated into the regression model to obtain unbiased estimating equations. METHODS: Robust Cox methods have been developed to better estimate associations when there are influential outliers in the exposure of interest, but these robust methods do not incorporate sampling weights. In this paper, we extend these robust methods, which already incorporate influence weights, so that they also accommodate sampling weights. RESULTS: Simulations illustrate that in the presence of influential outliers, the association estimate from the weighted robust method is closer to the true value than the estimate from traditional weighted Cox regression. As expected, in the absence of outliers, the use of robust methods yields a small loss of efficiency. Using data from a case-cohort study that is nested within the Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study, we illustrate differences between traditional and robust weighted Cox association estimates for the relationships between immune cell traits and risk of stroke. CONCLUSIONS: Robust weighted Cox regression methods are a new tool to analyze time-to-event data with sampling, e.g. case-cohort data, when exposures of interest contain outliers.
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Aterosclerose , Aterosclerose/diagnóstico , Estudos de Coortes , Humanos , Estudos Longitudinais , Modelos de Riscos Proporcionais , Análise de RegressãoRESUMO
We evaluated whether previously reported latent profiles of burnout among health-care workers (Leiter & Maslach, 2016) would generalize to a new sample of research and development (R&D) workers. We also extended recent reviews (e.g., Harari, Swider, Steed, & Breidenthal, 2018) by using a multilevel approach to the study of perfectionism and burnout in R&D teams in Taiwanese companies. Following a stress-generation model, we examined the association between perfectionistic strivings, perfectionistic concerns, and burnout based on data collected from 760 R&D employees and their 195 team leaders. The latent profiles that emerged differed more by level than kind; therefore, we implemented more parsimonious latent-variable modeling to test worker-level models involving perfectionistic strivings, concerns, and their interaction in predicting 3 dimensions of worker burnout. The latent interaction was significant only in the prediction of cynicism and revealed a general buffering effect of strivings on the negative effects of concerns. However, multilevel analyses that included leader perfectionism as a cross-level predictor revealed only conditional effects and no significant interactions. Overall, perfectionistic strivings had positive effects in association with lower levels of burnout, and perfectionistic concerns had negative effects and seemed to be a strong risk factor for burnout. High levels of perfectionistic concerns from leaders further increased the risk for 2 of the 3 dimensions of worker burnout. The results are discussed in light of theoretical and practical implications and future research into work-related contextual considerations, including culture and work environment, that might increase or decrease the effects of perfectionism on important outcomes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).