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A Family-Based Rare Haplotype Association Method for Quantitative Traits.


ABSTRACT: BACKGROUND:The variants identified in genome-wide association studies account for only a small fraction of disease heritability. A key to this "missing heritability" is believed to be rare variants. Specifically, we focus on rare haplotype variant (rHTV). The existing methods for detecting rHTV are mostly population-based, and as such, are susceptible to population stratification and admixture, leading to an inflated false-positive rate. Family-based methods are more robust in this respect. METHODS:We propose a method for detecting rHTVs associated with quantitative traits called family-based quantitative Bayesian LASSO (famQBL). FamQBL can analyze any type of pedigree and is based on a mixed model framework. We regularize the haplotype effects using Bayesian LASSO and estimate the posterior distributions using Markov chain Monte Carlo methods. RESULTS:We conduct simulation studies, including analyses of Genetic Analysis Workshop 18 simulated data, to study the properties of famQBL and compare with a standard family-based haplotype association test implemented in FBAT (family-based association test) software. We find famQBL to be more powerful than FBAT with well-controlled false-positive rates. We also apply famQBL to the Framingham Heart Study data and detect an rHTV associated with diastolic blood pressure. CONCLUSION:FamQBL can help uncover rHTVs associated with quantitative traits.

SUBMITTER: Datta AS 

PROVIDER: S-EPMC6521833 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A Family-Based Rare Haplotype Association Method for Quantitative Traits.

Datta Ananda S AS   Lin Shili S   Biswas Swati S  

Human heredity 20180101 4


<h4>Background</h4>The variants identified in genome-wide association studies account for only a small fraction of disease heritability. A key to this "missing heritability" is believed to be rare variants. Specifically, we focus on rare haplotype variant (rHTV). The existing methods for detecting rHTV are mostly population-based, and as such, are susceptible to population stratification and admixture, leading to an inflated false-positive rate. Family-based methods are more robust in this respe  ...[more]

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