Risk categorization for complex disorders according to genotype relative risk and precision in parameter estimates

2010 ◽  
Vol 34 (6) ◽  
pp. 624-632 ◽  
Author(s):  
Graham H.M. Goddard ◽  
Cathryn M. Lewis
Keyword(s):  
Relative Risk ◽  
Parameter Estimates ◽  
Genotype Relative Risk ◽  
Complex Disorders ◽  
Risk Categorization

scholarly journals Penalized generalized estimating equations for relative risk regression with applications to brain lesion data

2021 ◽  
Author(s):  
Petya Kindalova ◽  
Michele Veldsman ◽  
Thomas E Nichols ◽  
Ioannis Kosmidis
Keyword(s):  
Relative Risk ◽  
Generalized Estimating Equations ◽  
Binary Data ◽  
Large Scale ◽  
Brain Lesion ◽  
Estimating Equations ◽  
Variance Function ◽  
Parameter Estimates ◽  
Data Set ◽  
Generalized Estimating

Motivated by a brain lesion application, we introduce penalized generalized estimating equations for relative risk regression for modelling correlated binary data. Brain lesions can have varying incidence across the brain and result in both rare and high incidence outcomes. As a result, odds ratios estimated from generalized estimating equations with logistic regression structures are not necessarily directly interpretable as relative risks. On the other hand, use of log-link regression structures with the binomial variance function may lead to estimation instabilities when event probabilities are close to 1. To circumvent such issues, we use generalized estimating equations with log-link regression structures with identity variance function and unknown dispersion parameter. Even in this setting, parameter estimates can be infinite, which we address by penalizing the generalized estimating functions with the gradient of the Jeffreys prior. Our findings from extensive simulation studies show significant improvement over the standard log-link generalized estimating equations by providing finite estimates and achieving convergence when boundary estimates occur. The real data application on UK Biobank brain lesion maps further reveals the instabilities of the standard log-link generalized estimating equations for a large-scale data set and demonstrates the clear interpretation of relative risk in clinical applications.

Factor V Q506 (Resistance to Activated Protein C) and Prognosis after Acute Coronary Syndrome

1999 ◽  
Vol 81 (06) ◽  
pp. 857-860 ◽  
Author(s):  
Andreas Hillarp ◽  
Bengt Zöller ◽  
Leif Erhardt ◽  
Erik Berntorp ◽  
Björn Dahlbäck ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Relative Risk ◽  
Protein C ◽  
Proportional Hazards Model ◽  
Activated Protein C ◽  
Cox Proportional Hazards Model ◽  
Environment Interaction ◽  
Genotype Relative Risk ◽  
Coronary Syndrome ◽  
Increased Risk

SummaryFactor V:Q506 causing resistance to activated protein C (APC-resistance), is a risk factor for venous thrombosis. Some studies have indicated an association with arterial disease, especially in women. We investigated the prevalence of the FV:Q506 allele prospectively in 295 patients with acute coronary syndrome. Mortality and myocardial infarction rate were evaluated after 30 days and after 2 years. The FV:Q506 allele was found in 38 patients. In a Cox proportional hazards model, smokers carrying FV:Q506 had a higher risk of infarction or death within 30 days, compared to non-smokers with a normal genotype (relative risk 2.9 [95% CI 1.2-7.0]). The difference remained significant after 2 years (relative risk 2.8 [95% CI 1.2-6.5]). The effect of the FV:Q506 allele on clinical outcome in acute coronary syndrome has not previously been described. Our results demonstrate a gene-environment interaction between smoking and the FV:Q506 allele, with an increased risk of early complications after an acute ischemic event.

MDM2 SNP309 Is Associated With Poor Outcome in B-Cell Chronic Lymphocytic Leukemia

2008 ◽  
Vol 26 (14) ◽  
pp. 2252-2257 ◽  
Author(s):  
Irina Gryshchenko ◽  
Sebastian Hofbauer ◽  
Markus Stoecher ◽  
Peter T. Daniel ◽  
Michael Steurer ◽  
...  
Keyword(s):  
Relative Risk ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Gene Dosage ◽  
Lymphocytic Leukemia ◽  
Mdm2 Snp309 ◽  
Genotype Relative Risk ◽  
Mdm2 Expression ◽  
P53 Status ◽  
Cell Chronic Lymphocytic Leukemia

Purpose A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has been negatively associated with onset and outcome of disease in solid tumors. Because inactivation of p53 by deletion and/or mutations also impacts on the clinical course of B-cell chronic lymphocytic leukemia (B-CLL), we assessed the role of the SNP309 genotype in B-CLL. Patients and Methods The frequency of SNP309 T/T, T/G, or G/G genotypes and the p53 status (wild type, mutated, or deleted) were assessed and correlated with clinical outcome in 140 B-CLL patients and a second independent cohort. In addition, the correlation of the MDM2 SNP309 genotype with the MDM2 protein expression level in B-CLL cells was evaluated by immunoblotting. Results A significant negative association of the SNP309 T/G and G/G genotypes with overall survival was seen (T/G genotype, relative risk = 3.7; 95% CI, 1.2 to 11.5; P = .02; G/G genotype, relative risk = 9.1; 95% CI, 2.4 to 35.1; P = .001), but no correlation with incidence or onset of B-CLL was observed. The influence of the heterozygous SNP309 T/G genotype on treatment-free survival depended on the p53 status but not on the CD38, Zap-70, or IgVH mutational status or Rai stage of B-CLL patients. The unfavorable SNP309 T/G and G/G genotypes were associated with a gene-dosage–dependent increase of MDM2 expression. Conclusion The MDM2 SNP309 genotype influencing MDM2 expression levels was identified as an additional independent risk factor in B-CLL. Targeting MDM2-p53 interactions might emerge as a successful treatment strategy for B-CLL.

894: Incidence and Relative Risk of Sacral Neuromodulation Failure in Women with Voiding Dysfunction Status Post Hysterectomy

2006 ◽  
Vol 175 (4S) ◽  
pp. 289-289 ◽  
Author(s):  
Humphrey Atiemo ◽  
Ashwin A. Vaze ◽  
Courtenay K. Moore ◽  
Michael Aleman ◽  
Joseph Abdelmalak ◽  
...  
Keyword(s):  
Relative Risk ◽  
Voiding Dysfunction ◽  
Sacral Neuromodulation

193: The Relative Risk of Early Death from Comorbid Illnesses among Prostate Cancer Patients Receiving Curative Treatment

2005 ◽  
Vol 173 (4S) ◽  
pp. 53-53 ◽  
Author(s):  
Patti A. Groome ◽  
Susan L. Rohland ◽  
Michael D. Brundage ◽  
Jeremy P.W. Heaton ◽  
William J. Mackillop ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Relative Risk ◽  
Cancer Patients ◽  
Early Death ◽  
Curative Treatment

Benefits from Computerized Adaptive Testing as Seen in Simulation Studies

1999 ◽  
Vol 15 (2) ◽  
pp. 91-98 ◽  
Author(s):  
Lutz F. Hornke
Keyword(s):  
Measurement Error ◽  
Computerized Adaptive Testing ◽  
Test Procedure ◽  
Adaptive Testing ◽  
Parameter Estimates ◽  
Simulation Studies ◽  
Computerized Adaptive Test ◽  
Item Banks ◽  
Item Parameters ◽  
General Reliability

Summary: Item parameters for several hundreds of items were estimated based on empirical data from several thousands of subjects. The logistic one-parameter (1PL) and two-parameter (2PL) model estimates were evaluated. However, model fit showed that only a subset of items complied sufficiently, so that the remaining ones were assembled in well-fitting item banks. In several simulation studies 5000 simulated responses were generated in accordance with a computerized adaptive test procedure along with person parameters. A general reliability of .80 or a standard error of measurement of .44 was used as a stopping rule to end CAT testing. We also recorded how often each item was used by all simulees. Person-parameter estimates based on CAT correlated higher than .90 with true values simulated. For all 1PL fitting item banks most simulees used more than 20 items but less than 30 items to reach the pre-set level of measurement error. However, testing based on item banks that complied to the 2PL revealed that, on average, only 10 items were sufficient to end testing at the same measurement error level. Both clearly demonstrate the precision and economy of computerized adaptive testing. Empirical evaluations from everyday uses will show whether these trends will hold up in practice. If so, CAT will become possible and reasonable with some 150 well-calibrated 2PL items.

A Cautionary Note on Incremental Fit Indices Reported by LISREL

Methodology ◽  
2005 ◽  
Vol 1 (2) ◽  
pp. 81-85 ◽  
Author(s):  
Stefan C. Schmukle ◽  
Jochen Hardt
Keyword(s):  
Factor Analysis ◽  
Maximum Likelihood ◽  
Structural Equation ◽  
Structural Equation Models ◽  
Null Model ◽  
Likelihood Estimation ◽  
Parameter Estimates ◽  
Fit Indices ◽  
Cautionary Note ◽  
Confirmatory Factor

Abstract. Incremental fit indices (IFIs) are regularly used when assessing the fit of structural equation models. IFIs are based on the comparison of the fit of a target model with that of a null model. For maximum-likelihood estimation, IFIs are usually computed by using the χ2 statistics of the maximum-likelihood fitting function (ML-χ2). However, LISREL recently changed the computation of IFIs. Since version 8.52, IFIs reported by LISREL are based on the χ2 statistics of the reweighted least squares fitting function (RLS-χ2). Although both functions lead to the same maximum-likelihood parameter estimates, the two χ2 statistics reach different values. Because these differences are especially large for null models, IFIs are affected in particular. Consequently, RLS-χ2 based IFIs in combination with conventional cut-off values explored for ML-χ2 based IFIs may lead to a wrong acceptance of models. We demonstrate this point by a confirmatory factor analysis in a sample of 2449 subjects.

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