Reconsidering the asymptotic null distribution of likelihood ratio tests for genetic linkage in multivariate variance components models under complete pleiotropy

DOI10.1093/BIOSTATISTICS/KXP054zbMATH Open1437.62487arXiv0808.2000OpenAlexW2151197922WikidataQ33696486 ScholiaQ33696486MaRDI QIDQ3305014FDOQ3305014

Authors: Summer S. Han, Joseph T. Chang 

Publication date: 4 August 2020

Published in: Biostatistics (Search for Journal in Brave)

Abstract: Accurate knowledge of the null distribution of hypothesis tests is important for valid application of the tests. In previous papers and software, the asymptotic null distribution of likelihood ratio tests for detecting genetic linkage in multivariate variance components models has been stated to be a mixture of chi-square distributions with binomial mixing probabilities. Here we show, by simulation and by theoretical arguments based on the geometry of the parameter space, that all aspects of the previously stated asymptotic null distribution are incorrect--both the binomial mixing probabilities and the chi-square components. Correcting the null distribution gives more conservative critical values than previously stated, yielding P values that can easily be ten times larger. The true mixing probabilities give the highest probability to the case where all variance parameters are estimated positive, and the mixing components show severe departures from chi-square distributions. Thus, the asymptotic null distribution has complex features that raise challenges for the assessment of significance of multivariate linkage findings. We propose a method to generate an asymptotic null distribution that is much faster than other empirical methods such as gene-dropping, enabling us to obtain P values with higher precision more efficiently.

Full work available at URL: https://arxiv.org/abs/0808.2000

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Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10)

Cites Work

• Asymptotic Properties of Maximum Likelihood Estimators and Likelihood Ratio Tests Under Nonstandard Conditions
• Genetic linkage methods for quantitative traits

Cited In (2)

• Calculating asymptotic significance levels of the constrained likelihood ratio test with application to multivariate genetic linkage analysis
• Assessing statistical significance in variance components linkage analysis: a theoretical justification

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