Biomaterial Database

Ascertainment adjustment in complex diseases. 2002

David V Glidden, and Kung-Yee Liang

Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California 94143-0560, USA. david@biostat.ucsf.edu

Genetic studies of complex diseases must confront two statistically difficult issues simultaneously. First, in many settings, to minimize the number of individuals to be genotyped, families enriched for disease must be oversampled. Also, statistical models in family studies should allow for residual association. This association will represent unmeasured genetic and environmental factors influencing disease risk. Dealing with these features simultaneously is both compelling and challenging. Burton et al. [2000] (Am. J. Hum. Gen. 69: 1505-14) recently discussed this issue and suggested that ascertainment corrections may lead to problematic parameter estimation. We revisit the issues and examples of Burton et al. [2000] (Am. J. Hum. Genet. 69: 1505-14) and present a more optimistic assessment. Estimation in this context is conceptually straightforward, but may be more problematic in practice. Specifically, we find that even slight misspecification of the random effects distribution in ascertainment-adjusted likelihood can yield severely biased parameter estimates. This result should make scientists wary when interpreting results from ascertainment-adjusted variance-component models. .

UI	MeSH Term	Description	Entries
D005820	Genetic Testing	Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.	Genetic Predisposition Testing,Genetic Screening,Predictive Genetic Testing,Predictive Testing, Genetic,Testing, Genetic Predisposition,Genetic Predictive Testing,Genetic Screenings,Genetic Testing, Predictive,Predisposition Testing, Genetic,Screening, Genetic,Screenings, Genetic,Testing, Genetic,Testing, Genetic Predictive,Testing, Predictive Genetic
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006580	Genetic Carrier Screening	Identification of individuals who are heterozygous at a GENETIC LOCUS for a recessive PHENOTYPE.	Carriers, Genetic, Detection,Genetic Carriers, Detection,Heterozygote Detection,Carrier Detection, Genetic,Detection, Genetic Carrier,Genetic Carrier Detection,Heterozygote Screening,Carrier Screening, Genetic,Detection, Heterozygote,Screening, Genetic Carrier,Screening, Heterozygote,Screenings, Genetic Carrier
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015233	Models, Statistical	Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.	Probabilistic Models,Statistical Models,Two-Parameter Models,Model, Statistical,Models, Binomial,Models, Polynomial,Statistical Model,Binomial Model,Binomial Models,Model, Binomial,Model, Polynomial,Model, Probabilistic,Model, Two-Parameter,Models, Probabilistic,Models, Two-Parameter,Polynomial Model,Polynomial Models,Probabilistic Model,Two Parameter Models,Two-Parameter Model
D015982	Bias	Any deviation of results or inferences from the truth, or processes leading to such deviation. Bias can result from several sources: one-sided or systematic variations in measurement from the true value (systematic error); flaws in study design; deviation of inferences, interpretations, or analyses based on flawed data or data collection; etc. There is no sense of prejudice or subjectivity implied in the assessment of bias under these conditions.	Aggregation Bias,Bias, Aggregation,Bias, Ecological,Bias, Statistical,Bias, Systematic,Ecological Bias,Outcome Measurement Errors,Statistical Bias,Systematic Bias,Bias, Epidemiologic,Biases,Biases, Ecological,Biases, Statistical,Ecological Biases,Ecological Fallacies,Ecological Fallacy,Epidemiologic Biases,Experimental Bias,Fallacies, Ecological,Fallacy, Ecological,Scientific Bias,Statistical Biases,Truncation Bias,Truncation Biases,Bias, Experimental,Bias, Scientific,Bias, Truncation,Biase, Epidemiologic,Biases, Epidemiologic,Biases, Truncation,Epidemiologic Biase,Error, Outcome Measurement,Errors, Outcome Measurement,Outcome Measurement Error
D016013	Likelihood Functions	Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters.	Likelihood Ratio Test,Maximum Likelihood Estimates,Estimate, Maximum Likelihood,Estimates, Maximum Likelihood,Function, Likelihood,Functions, Likelihood,Likelihood Function,Maximum Likelihood Estimate,Test, Likelihood Ratio
D018570	Risk Assessment	The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)	Assessment, Risk,Benefit-Risk Assessment,Risk Analysis,Risk-Benefit Assessment,Health Risk Assessment,Risks and Benefits,Analysis, Risk,Assessment, Benefit-Risk,Assessment, Health Risk,Assessment, Risk-Benefit,Benefit Risk Assessment,Benefit-Risk Assessments,Benefits and Risks,Health Risk Assessments,Risk Analyses,Risk Assessment, Health,Risk Assessments,Risk Benefit Assessment,Risk-Benefit Assessments
D020022	Genetic Predisposition to Disease	A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.	Genetic Predisposition,Genetic Susceptibility,Predisposition, Genetic,Susceptibility, Genetic,Genetic Predispositions,Genetic Susceptibilities,Predispositions, Genetic,Susceptibilities, Genetic
D030342	Genetic Diseases, Inborn	Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.	Hereditary Diseases,Genetic Diseases,Genetic Disorders,Hereditary Disease,Inborn Genetic Diseases,Single-Gene Defects,Defect, Single-Gene,Defects, Single-Gene,Disease, Genetic,Disease, Hereditary,Disease, Inborn Genetic,Diseases, Genetic,Diseases, Hereditary,Diseases, Inborn Genetic,Disorder, Genetic,Disorders, Genetic,Genetic Disease,Genetic Disease, Inborn,Genetic Disorder,Inborn Genetic Disease,Single Gene Defects,Single-Gene Defect