Generalization of Rare Variant Association Tests for Longitudinal Family Studies

Genetic Epidemiology
Li-Chu ChienYen-Feng Chiu

Abstract

Given the functional relevance of many rare variants, their identification is frequently critical for dissecting disease etiology. Functional variants are likely to be aggregated in family studies enriched with affected members, and this aggregation increases the statistical power to detect rare variants associated with a trait of interest. Longitudinal family studies provide additional information for identifying genetic and environmental factors associated with disease over time. However, methods to analyze rare variants in longitudinal family data remain fairly limited. These methods should be capable of accounting for different sources of correlations and handling large amounts of sequencing data efficiently. To identify rare variants associated with a phenotype in longitudinal family studies, we extended pedigree-based burden (BT) and kernel (KS) association tests to genetic longitudinal studies. Generalized estimating equation (GEE) approaches were used to generalize the pedigree-based BT and KS to multiple correlated phenotypes under the generalized linear model framework, adjusting for fixed effects of confounding factors. These tests accounted for complex correlations between repeated measures of the same phenotype (se...Continue Reading

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Citations

Sep 7, 2018·Genetic Epidemiology·Li-Chu Chien, Yen-Feng Chiu
Jul 23, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Jill M JohnsenUNKNOWN Members of Working Group 4, the NHLBI State of the Science Workshop on Factor VIII Inhibitors: Generating a National Bluepri
Nov 20, 2016·Genetic Epidemiology·Zhong WangZuoheng Wang

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