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Identification of the associations between genes and quantitative traits using entropy-based kernel density estimation.

ABSTRACT: Genetic associations have been quantified using a number of statistical measures. Entropy-based mutual information may be one of the more direct ways of estimating the association, in the sense that it does not depend on the parametrization. For this purpose, both the entropy and conditional entropy of the phenotype distribution should be obtained. Quantitative traits, however, do not usually allow an exact evaluation of entropy. The estimation of entropy needs a probability density function, which can be approximated by kernel density estimation. We have investigated the proper sequence of procedures for combining the kernel density estimation and entropy estimation with a probability density function in order to calculate mutual information. Genotypes and their interactions were constructed to set the conditions for conditional entropy. Extensive simulation data created using three types of generating functions were analyzed using two different kernels as well as two types of multifactor dimensionality reduction and another probability density approximation method called m-spacing. The statistical power in terms of correct detection rates was compared. Using kernels was found to be most useful when the trait distributions were more complex than simple normal or gamma distributions. A full-scale genomic dataset was explored to identify associations using the 2-h oral glucose tolerance test results and γ-glutamyl transpeptidase levels as phenotypes. Clearly distinguishable single-nucleotide polymorphisms (SNPs) and interacting SNP pairs associated with these phenotypes were found and listed with empirical p-values.

SUBMITTER: Yee J

PROVIDER: S-EPMC9299569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLocal destinations have previously been shown to be associated with higher levels of both physical activity and walking, but little is known about how the distribution of destinations is related to activity. Kernel density estimation is a spatial analysis technique that accounts for the location of features relative to each other. Using kernel density estimation, this study sought to investigate whether individuals who live near destinations (shops and service facilities) that are more intensely distributed rather than dispersed: 1) have higher odds of being sufficiently active; 2) engage in more frequent walking for transport and recreation.MethodsThe sample consisted of 2349 residents of 50 urban areas in metropolitan Melbourne, Australia. Destinations within these areas were geocoded and kernel density estimates of destination intensity were created using kernels of 400m (meters), 800m and 1200m. Using multilevel logistic regression, the association between destination intensity (classified in quintiles Q1(least)-Q5(most)) and likelihood of: 1) being sufficiently active (compared to insufficiently active); 2) walking≥4/week (at least 4 times per week, compared to walking less), was estimated in models that were adjusted for potential confounders.ResultsFor all kernel distances, there was a significantly greater likelihood of walking≥4/week, among respondents living in areas of greatest destinations intensity compared to areas with least destination intensity: 400m (Q4 OR 1.41 95%CI 1.02-1.96; Q5 OR 1.49 95%CI 1.06-2.09), 800m (Q4 OR 1.55, 95%CI 1.09-2.21; Q5, OR 1.71, 95%CI 1.18-2.48) and 1200m (Q4, OR 1.7, 95%CI 1.18-2.45; Q5, OR 1.86 95%CI 1.28-2.71). There was also evidence of associations between destination intensity and sufficient physical activity, however these associations were markedly attenuated when walking was included in the models.ConclusionsThis study, conducted within urban Melbourne, found that those who lived in areas of greater destination intensity walked more frequently, and showed higher odds of being sufficiently physically active-an effect that was largely explained by levels of walking. The results suggest that increasing the intensity of destinations in areas where they are more dispersed; and or planning neighborhoods with greater destination intensity, may increase residents' likelihood of being sufficiently active for health.

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Identification of the associations between genes and quantitative traits using entropy-based kernel density estimation.

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