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Ascertainment Bias (ascertainment + bias)
Selected AbstractsStatistical Inference for Familial Disease ClustersBIOMETRICS, Issue 3 2002Chang Yu Summary. In many epidemiologic studies, the first indication of an environmental or genetic contribution to the disease is the way in which the diseased cases cluster within the same family units. The concept of clustering is contrasted with incidence. We assume that all individuals are exchangeable except for their disease status. This assumption is used to provide an exact test of the initial hypothesis of no familial link with the disease, conditional on the number of diseased cases and the distribution of the sizes of the various family units. New parametric generalizations of binomial sampling models are described to provide measures of the effect size of the disease clustering. We consider models and an example that takes covariates into account. Ascertainment bias is described and the appropriate sampling distribution is demonstrated. Four numerical examples with real data illustrate these methods. [source] Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian familiesEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2009M. A. C. Saporta Background and purpose:, Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. Methods:, Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. Results:, Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66,99) after 60 years. Conclusion:, Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population. [source] PEL: an unbiased method for estimating age-dependent genetic disease risk from pedigree data unselected for family historyGENETIC EPIDEMIOLOGY, Issue 5 2009F. Alarcon Abstract Providing valid risk estimates of a genetic disease with variable age of onset is a major challenge for prevention strategies. When data are obtained from pedigrees ascertained through affected individuals, an adjustment for ascertainment bias is necessary. This article focuses on ascertainment through at least one affected and presents an estimation method based on maximum likelihood, called the Proband's phenotype exclusion likelihood or PEL for estimating age-dependent penetrance using disease status and genotypic information of family members in pedigrees unselected for family history. We studied the properties of the PEL and compared with another method, the prospective likelihood, in terms of bias and efficiency in risk estimate. For that purpose, family samples were simulated under various disease risk models and under various ascertainment patterns. We showed that, whatever the genetic model and the ascertainment scheme, the PEL provided unbiased estimates, whereas the prospective likelihood exhibited some bias in a number of situations. As an illustration, we estimated the disease risk for transthyretin amyloid neuropathy from a French sample and a Portuguese sample and for BRCA1/2 associated breast cancer from a sample ascertained on early-onset breast cancer cases. Genet. Epidemiol. 33:379,385, 2009. © 2008 Wiley-Liss, Inc. [source] The University of California, San Francisco Family Alcoholism Study.ALCOHOLISM, Issue 10 2004Background: The University of California, San Francisco (UCSF) Family Alcoholism Study is a project designed to identify genetic loci that influence susceptibility to alcohol dependence and related phenotypes. Evidence supports a substantial genetic contribution to alcoholism susceptibility. However, the genetic epidemiology of alcoholism is complex, and its clinical manifestation is heterogeneous, making phenotype definition and demonstration of linkage difficult. Despite these challenges, some progress has been made toward identifying genes. Methods: The UCSF Family Alcoholism Study used a small family design, focusing primarily on sibling pairs and parent-child trios for linkage and association studies. Alcoholism-related phenotypes were assessed through interview and self-report questionnaires, with a focus on unidimensional and subphenotypical traits. Data-driven approaches to determining the most promising phenotypes for genetic analysis are being used. Both genome-wide scan and candidate gene approaches were used. Results: The study enrolled 2154 individuals from 970 families from December 1995 through January 2003. Test-retest and interrater reliability for clinical data are very good, and power estimates suggest that this study will have adequate power by linkage analysis to detect loci with moderate effects. Design, methods, and sample demographics of the UCSF Family Study are presented, along with intrafamilial correlations for primary diagnostic phenotypes. Conclusions: Plans for genetic analysis, novel approaches to phenotype refinement, and the implications of ascertainment bias for heritability estimates are discussed. [source] The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up dataBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2005I. Man Summary Background, Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans. Objectives, To determine the skin cancer incidence in a population treated with TL-01 phototherapy. Patients and methods, All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex. Results, Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0·04,13). The median cumulative number of TL-01 treatments and dose were 23 (1,199) and 13 337 (30,284 415) mJ cm,2, respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4·7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102,391); P < 0·05]. Conclusions, A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential. [source] Corticosteroid-binding globulin gene polymorphisms: clinical implications and links to idiopathic chronic fatigue disordersCLINICAL ENDOCRINOLOGY, Issue 2 2007D. J. Torpy Summary Corticosteroid-binding globulin (CBG) binds cortisol with high affinity, facilitating transport of cortisol in blood, although tissue-specific CBG,cortisol interactions have long been postulated. There are three heritable, human CBG gene mutations that can reduce CBG,cortisol binding affinity and/or reduce circulating CBG levels. In some families, fatigue and low blood pressure have been associated with affinity altering or CBG level reducing mutations. The limited numbers of reports raise the possibility of ascertainment bias as many cases presented with features suggesting cortisol deficiency. The recent description of a genetically CBG-deficient mouse listed fatigue, manifest as reduced activity levels, as part of the phenotype, which also included immune aberrations. Severe CBG mutations may produce fatigue, but one study suggests that these are a rare cause of idiopathic fatigue. A mechanism for the effect of CBG mutations on fatigue is not readily apparent because free cortisol levels are normal, although we speculate that CBG may have an effect on cortisol,brain transport. [source] |