Robust LOD scores for variance component-based linkage analysis

Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

“…Also, the use of postbronchodilator measurements for linkage analysis has been suggested to decrease the heterogeneity of spirometric measures (2). Importantly, variance component linkage analysis can be influenced by kurtosis of the phenotype distributions, with kurtosis being a main determinant of the effect of non-normality on the likelihood ratio test statistic (34). However, none of our results demonstrated kurtosis greater than 2; simulations were highly significant, and results remained robust when analyzed using the "t" distribution.…”

Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

“…Also, the use of postbronchodilator measurements for linkage analysis has been suggested to decrease the heterogeneity of spirometric measures (2). Importantly, variance component linkage analysis can be influenced by kurtosis of the phenotype distributions, with kurtosis being a main determinant of the effect of non-normality on the likelihood ratio test statistic (34). However, none of our results demonstrated kurtosis greater than 2; simulations were highly significant, and results remained robust when analyzed using the "t" distribution.…”

A rare variant association test in family‐based designs and non‐normal quantitative traits

“…However, all these quantitative trait methods for association are based on the assumption of multivariate normality of the phenotype within a family, and violation of this assumption may yield a type I error inflation or a significant loss of power. Such a phenomenon has been shown in similar models in variance-component linkage analysis of quantitative trait loci [23][24][25].…”

A Major Locus for Fasting Insulin Concentrations and Insulin Resistance on Chromosome 6q with Strong Pleiotropic Effects on Obesity-Related Phenotypes in Nondiabetic Mexican Americans

“…For the phenotypes used in this study, the coefficient of kurtosis ranged from Ϫ0.9 (ln HOMA %S) to 1.6 (LEPT). Nonetheless, as an added precaution, in addition to the reported empirical P values to support our findings, we used a robust statistical approach to verify our original univariate linkage findings (Blangero et al 2000(Blangero et al , 2001. For a given phenotype, we obtained the empirical distribution for the LOD scores by simulation as described earlier.…”

“…The pedigree-based variance-component approach (the approach used in the present study) has been shown to be a powerful technique for linkage analysis (Almasy and Blangero 1998;Pratt et al 2000). However, since this technique is based on the assumption of multivariate normal distribution, there has been continued interest in its sensitivity to violations of this assumption (Allison et al 1999;Blangero et al 2000). In general, this approach has been shown to be robust to such violations (Beaty et al 1985;Amos 1994), although some types of nonnormality (e.g., leptokurtosis) could result in inflated type I-error rates (Allison et al 1999;Blangero et al 2000Blangero et al , 2001.…”

Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

“…Also, the use of postbronchodilator measurements for linkage analysis has been suggested to decrease the heterogeneity of spirometric measures (2). Importantly, variance component linkage analysis can be influenced by kurtosis of the phenotype distributions, with kurtosis being a main determinant of the effect of non-normality on the likelihood ratio test statistic (34). However, none of our results demonstrated kurtosis greater than 2; simulations were highly significant, and results remained robust when analyzed using the "t" distribution.…”

A rare variant association test in family‐based designs and non‐normal quantitative traits

“…However, all these quantitative trait methods for association are based on the assumption of multivariate normality of the phenotype within a family, and violation of this assumption may yield a type I error inflation or a significant loss of power. Such a phenomenon has been shown in similar models in variance-component linkage analysis of quantitative trait loci [23][24][25].…”

A Major Locus for Fasting Insulin Concentrations and Insulin Resistance on Chromosome 6q with Strong Pleiotropic Effects on Obesity-Related Phenotypes in Nondiabetic Mexican Americans

“…For the phenotypes used in this study, the coefficient of kurtosis ranged from Ϫ0.9 (ln HOMA %S) to 1.6 (LEPT). Nonetheless, as an added precaution, in addition to the reported empirical P values to support our findings, we used a robust statistical approach to verify our original univariate linkage findings (Blangero et al 2000(Blangero et al , 2001. For a given phenotype, we obtained the empirical distribution for the LOD scores by simulation as described earlier.…”

“…The pedigree-based variance-component approach (the approach used in the present study) has been shown to be a powerful technique for linkage analysis (Almasy and Blangero 1998;Pratt et al 2000). However, since this technique is based on the assumption of multivariate normal distribution, there has been continued interest in its sensitivity to violations of this assumption (Allison et al 1999;Blangero et al 2000). In general, this approach has been shown to be robust to such violations (Beaty et al 1985;Amos 1994), although some types of nonnormality (e.g., leptokurtosis) could result in inflated type I-error rates (Allison et al 1999;Blangero et al 2000Blangero et al , 2001.…”

Genome-wide Linkage of Forced Mid-expiratory Flow in Chronic Obstructive Pulmonary Disease

“…Also, the use of postbronchodilator measurements for linkage analysis has been suggested to decrease the heterogeneity of spirometric measures (2). Importantly, variance component linkage analysis can be influenced by kurtosis of the phenotype distributions, with kurtosis being a main determinant of the effect of non-normality on the likelihood ratio test statistic (34). However, none of our results demonstrated kurtosis greater than 2; simulations were highly significant, and results remained robust when analyzed using the "t" distribution.…”

A rare variant association test in family‐based designs and non‐normal quantitative traits

“…However, all these quantitative trait methods for association are based on the assumption of multivariate normality of the phenotype within a family, and violation of this assumption may yield a type I error inflation or a significant loss of power. Such a phenomenon has been shown in similar models in variance-component linkage analysis of quantitative trait loci [23][24][25].…”

A Major Locus for Fasting Insulin Concentrations and Insulin Resistance on Chromosome 6q with Strong Pleiotropic Effects on Obesity-Related Phenotypes in Nondiabetic Mexican Americans

“…For the phenotypes used in this study, the coefficient of kurtosis ranged from Ϫ0.9 (ln HOMA %S) to 1.6 (LEPT). Nonetheless, as an added precaution, in addition to the reported empirical P values to support our findings, we used a robust statistical approach to verify our original univariate linkage findings (Blangero et al 2000(Blangero et al , 2001. For a given phenotype, we obtained the empirical distribution for the LOD scores by simulation as described earlier.…”

“…The pedigree-based variance-component approach (the approach used in the present study) has been shown to be a powerful technique for linkage analysis (Almasy and Blangero 1998;Pratt et al 2000). However, since this technique is based on the assumption of multivariate normal distribution, there has been continued interest in its sensitivity to violations of this assumption (Allison et al 1999;Blangero et al 2000). In general, this approach has been shown to be robust to such violations (Beaty et al 1985;Amos 1994), although some types of nonnormality (e.g., leptokurtosis) could result in inflated type I-error rates (Allison et al 1999;Blangero et al 2000Blangero et al , 2001.…”