Adaptive Combination of P-values to Analyze Case-Parent Trios
Date Issued
2015
Date
2015
Author(s)
Liang, Yun-Chieh
Abstract
As the development of next-generation sequencing technologies, geneticists found that rare causal variants (minor allele frequency (MAF) < 1%) detection can help to uncover the etiology of complex diseases. Recruiting case-parent trios is a simple and popular study design in family-based studies. If researchers can also obtain data from population controls, utilizing unrelated controls in trios can improve the power of a statistical method. The transmission disequilibrium test (TDT) is a well-known method to analyze case-parent trio data. It has been extended to rare-variant association testing (referred to as ‘rvTDT’ hereafter), and is robust to population stratification because of its conditioning approach. However, power loss may occur in the conditioning process. We here propose a ‘conditioning adaptive combination of P-values method’ (abbreviated as ‘conADA’). By first truncating the variants with larger P-values, it is robust to the inclusion of neutral variants. Moreover, because the test statistic is developed by conditioning on parental genotypes, conADA generates valid statistical inference in the presence of population stratification.
Subjects
Neutral variants
next-generation sequencing
affected offspring
rare variants
Type
thesis
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