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  • Author: J. M. Haynes x
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Phenotype and/or genotype misclassification can: significantly increase type II error probabilities for genetic case/control association, causing decrease in statistical power; and produce inaccurate estimates of population frequency parameters. We present a method, the likelihood ratio test allowing for errors (LRTae) that incorporates double-sample information for phenotypes and/or genotypes on a sub-sample of cases/controls. Population frequency parameters and misclassification probabilities are determined using a double-sample procedure as implemented in the Expectation-Maximization (EM) method. We perform null simulations assuming a SNP marker or a 4-allele (multi-allele) marker locus. To compare our method with the standard method that makes no adjustment for errors (LRTstd), we perform power simulations using a 2^k factorial design with high and low settings of: case/control samples, phenotype/genotype costs, double-sampled phenotypes/genotypes costs, phenotype/genotype error, and proportions of double-sampled individuals. All power simulations are performed fixing equal costs for the LRTstd and LRTae methods. We also consider case/control ApoE genotype data for an actual Alzheimer's study.The LRTae method maintains correct type I error proportions for all null simulations and all significance level thresholds (10%, 5%, 1%). LRTae average estimates of population frequencies and misclassification probabilities are equal to the true values, with variances of 10e-7 to 10e-8. For power simulations, the median power difference LRTae-LRTstd at the 5% significance level is 0.06 for multi-allele data and 0.01 for SNP data. For the ApoE data example, the LRTae and LRTstd p-values are 5.8 x 10e-5 and 1.6 x 10e-3, respectively. The increase in significance is due to adjustment in the LRTae for misclassification of the most commonly reported risk allele. We have developed freely available software that performs our LRTae statistic.

Abstract

The advent of functional magnetic resonance imaging (fMRI) of brain function 20 years ago has provided a new methodology for non-in­vasive measurement of brain function that is now widely used in cognitive neurosci­ence. Traditionally, fMRI data has been an­alyzed looking for overall activity chang­es in brain regions in response to a stimu­lus or a cognitive task. Now, recent develop­ments have introduced more elaborate, con­tent-based analysis techniques. When mul­tivariate decoding is applied to the detailed patterning of regionally-specific fMRI signals, it can be used to assess the amount of infor­mation these encode about specific task-vari­ables. Here we provide an overview of sev­eral developments, spanning from applica­tions in cognitive neuroscience (perception, attention, reward, decision making, emotion­al communication) to methodology (informa­tion flow, surface-based searchlight decod­ing) and medical diagnostics.

Recommendations are given for reporting in the primary scientific literature of measurements involving phase equilibrium. The focus is on documentation issues, and many of the recommendations may also be applied to the more general fields of thermodynamic and transport properties. The historical context of the work and specific plans for implementation of the recommendations are discussed.