Power of Linkage versus Association Analysis of Quantitative Traits, by Use of Variance-Components Models, for Sibship Data

• Published in: American journal of human genetics Vol. 66; no. 5; pp. 1616 - 1630
• Main Authors: Sham, P.C., Cherny, S.S., Purcell, S., Hewitt, J.K.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Chicago, IL Elsevier Inc 01.05.2000; University of Chicago Press
• Subjects: Association; Biological and medical sciences; Chi-Square Distribution; Chromosome Mapping - methods; Chromosome Mapping - statistics & numerical data; Computer Simulation; Gene Frequency - genetics; General aspects. Genetic counseling; Genetic Markers - genetics; Genetic Variation - genetics; Genotype; Haplotypes - genetics; Humans; Likelihood Functions; Linkage Disequilibrium; Lod Score; Matched-Pair Analysis; Medical genetics; Medical sciences; Models, Genetic; Nuclear Family; Power; Quantitative Trait, Heritable; Quantitative-trait locus/loci; Sample Size; Variance-components analysis; Association; Linkage disequilibrium; Variance-components analysis; Power; Quantitative-trait locus/loci; Human; Linkage; Family study; Exploration; Linkage equilibrium; Statistics; Genetic determinism; Statistical test; Phenotype; Analysis method; Genetics; Variance component; Comparative study
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/302891

Optimal design of quantitative-trait loci (QTL) mapping studies requires a precise understanding of the power of QTL linkage versus QTL association analysis, under a range of different conditions. In this article, we investigate the power of QTL linkage and association analyses for simple random sibship samples, under the variance-components model proposed by Fulker et al. After a brief description of an extension of this variance-components model, we show that the powers of both linkage and association analyses are crucially dependent on the proportion of phenotypic variance attributable to the QTL. The main difference between the two tests is that, whereas the power of association is directly related to the QTL heritability, the power of linkage is related more closely to the square of the QTL heritability. We also describe both how the power of linkage is attenuated by incomplete linkage and incomplete marker information and how the power of association is attenuated by incomplete linkage disequilibrium.