The genetic interpretation of area under the ROC curve in genomic profiling. 2010

Naomi R Wray, and Jian Yang, and Michael E Goddard, and Peter M Visscher
Genetic Epidemiology and Queensland Statistical Genetics, Queensland Institute of Medical Research, Brisbane, Australia. Naomi.Wray@qimr.edu.au

Genome-wide association studies in human populations have facilitated the creation of genomic profiles which combine the effects of many associated genetic variants to predict risk of disease. The area under the receiver operator characteristic (ROC) curve is a well established measure for determining the efficacy of tests in correctly classifying diseased and non-diseased individuals. We use quantitative genetics theory to provide insight into the genetic interpretation of the area under the ROC curve (AUC) when the test classifier is a predictor of genetic risk. Even when the proportion of genetic variance explained by the test is 100%, there is a maximum value for AUC that depends on the genetic epidemiology of the disease, i.e. either the sibling recurrence risk or heritability and disease prevalence. We derive an equation relating maximum AUC to heritability and disease prevalence. The expression can be reversed to calculate the proportion of genetic variance explained given AUC, disease prevalence, and heritability. We use published estimates of disease prevalence and sibling recurrence risk for 17 complex genetic diseases to calculate the proportion of genetic variance that a test must explain to achieve AUC = 0.75; this varied from 0.10 to 0.74. We provide a genetic interpretation of AUC for use with predictors of genetic risk based on genomic profiles. We provide a strategy to estimate proportion of genetic variance explained on the liability scale from estimates of AUC, disease prevalence, and heritability (or sibling recurrence risk) available as an online calculator.

UI MeSH Term Description Entries
D008268 Macular Degeneration Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms. Maculopathy,Maculopathy, Age-Related,Age-Related Macular Degeneration,Age-Related Maculopathies,Age-Related Maculopathy,Macular Degeneration, Age-Related,Macular Dystrophy,Maculopathies, Age-Related,Age Related Macular Degeneration,Age Related Maculopathies,Age Related Maculopathy,Age-Related Macular Degenerations,Degeneration, Macular,Dystrophy, Macular,Macular Degeneration, Age Related,Macular Degenerations,Macular Dystrophies,Maculopathies,Maculopathy, Age Related
D004194 Disease A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown. Diseases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old
D012372 ROC Curve A graphic means for assessing the ability of a screening test to discriminate between healthy and diseased persons; may also be used in other studies, e.g., distinguishing stimuli responses as to a faint stimuli or nonstimuli. ROC Analysis,Receiver Operating Characteristic,Analysis, ROC,Analyses, ROC,Characteristic, Receiver Operating,Characteristics, Receiver Operating,Curve, ROC,Curves, ROC,ROC Analyses,ROC Curves,Receiver Operating Characteristics
D015894 Genome, Human The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs. Human Genome,Genomes, Human,Human Genomes
D015995 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time. Period Prevalence,Point Prevalence,Period Prevalences,Point Prevalences,Prevalence, Period,Prevalence, Point,Prevalences
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area
D020869 Gene Expression Profiling The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell. Gene Expression Analysis,Gene Expression Pattern Analysis,Transcript Expression Analysis,Transcriptome Profiling,Transcriptomics,mRNA Differential Display,Gene Expression Monitoring,Transcriptome Analysis,Analyses, Gene Expression,Analyses, Transcript Expression,Analyses, Transcriptome,Analysis, Gene Expression,Analysis, Transcript Expression,Analysis, Transcriptome,Differential Display, mRNA,Differential Displays, mRNA,Expression Analyses, Gene,Expression Analysis, Gene,Gene Expression Analyses,Gene Expression Monitorings,Gene Expression Profilings,Monitoring, Gene Expression,Monitorings, Gene Expression,Profiling, Gene Expression,Profiling, Transcriptome,Profilings, Gene Expression,Profilings, Transcriptome,Transcript Expression Analyses,Transcriptome Analyses,Transcriptome Profilings,mRNA Differential Displays
D040582 Inheritance Patterns The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION. Inheritance Pattern,Pattern, Inheritance,Patterns, Inheritance

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