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S. Hora (1986)
Statistical Inference Based on RanksTechnometrics, 28
M. Stoesz, J. Cohen, V. Mooser, S. Marcovina, R. Guerra (1997)
Extension of the Haseman–Elston method to multiple alleles and multiple loci: theory and practice for candidate genesAnnals of Human Genetics, 61
We are grateful to the referees for their suggestions in improving the article. This work was supported by National Institutes of Health grant
R. Guerra, Jinping Wang, S. Grundy, J. Cohen (1997)
A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol.Proceedings of the National Academy of Sciences of the United States of America, 94 9
M. Stoesz, J. Cohen, V. Mooser, S. Marcovina, R. Guerra (1997)
Extension of the Haseman-Elston method to multiple alleles and multiple lociAnnals of Human Genetics, 61
L. Kruglyak, E. Lander (1995)
Complete multipoint sib-pair analysis of qualitative and quantitative traits.American journal of human genetics, 57 2
R. Fisher
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Jonathan Cohen, Zifen Wang, S. Grundy, M. Stoesz, R. Guerra (1994)
Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels.The Journal of clinical investigation, 94 6
E. Boerwinkle, S. Visvikis, Dorothy Welsh, J. Steinmetz, S. Hanash, C. Sing, J. Opitz, J. Reynolds (1987)
The use of measured genotype information in the analysis of quantitative phenotypes in man. II. The role of the apolipoprotein E polymorphism in determining levels, variability, and covariability of cholesterol, betalipoprotein, and triglycerides in a sample of unrelated individuals.American journal of medical genetics, 27 3
Let Y i denote a squared (or absolute) phenotypic difference of two siblings sharing i alleles ibd
J. Haseman, R. Elston (1972)
The investigation of linkage between a quantitative trait and a marker locusBehavior Genetics, 2
L. Penrose
THE CORRELATION BETWEEN RELATIVES ON THE SUPPOSITION OF MENDELIAN INHERITANCE
Y. Wan, Jonathan Cohen, Rudy Guerra (1997)
A permutation test for the robust sib‐pair linkage methodAnnals of Human Genetics, 61
E. Boerwinkle, C. Sing (1987)
The use of measured genotype information in the analysis of quantitative phenotypes in man.Annals of Human Genetics, 51
Many traits that distinguish one individual from another, such as height or weight, are clearly heritable and yet vary continuously in populations. Continuous, heritable variation in trait levels presumably reflects the segregation of multiple genes, but elucidation of the genetic architecture of quantitative traits has been limited. Haseman & Elston (1972) developed a genetically robust method (HE) for detecting linkage to quantitative trait loci using sib‐pairs. The method is based on a simple linear regression of the squared sib‐pairs trait difference on the proportion of alleles shared identical by descent at a marker locus. Linkage is detected by a negative slope which has been traditionally assessed by a standard t‐test. Wan, Cohen & Guerra (1997) have shown that the standard t‐test is robust to the violations of the stochastic assumptions underlying the test. In practice, however, the standard t‐test, based on least‐squares regression, is sensitive to outliers. The presence of outliers in the data can lead to false positive and false negative linkage results. Accordingly we have developed and evaluated a statistically robust procedure for the HE approach to linkage. The procedure is based on robust regression. Simulation studies show that this robust procedure has greater power than the standard t‐test in the presence of outliers, and has similar power to the standard t‐test in the absence of outliers. This robust procedure also shows greater power than rank‐based approaches either in the absence or presence of outliers. To illustrate the methods using real data we reanalyse data from two lipoprotein systems that motivated this work.
Annals of Human Genetics – Wiley
Published: Jan 1, 1998
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