A Family-Based Rare Haplotype Association Method for Quantitative Traits

Overview

Journal Hum Hered

Specialty Genetics

Date 2019 Feb 26

PMID 30799419

Citations 3

Authors

Ananda S Datta

Shili Lin

Swati Biswas

Affiliations

Soon will be listed here.

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.

Citing Articles

Bivariate quantitative Bayesian LASSO for detecting association of rare haplotypes with two correlated continuous phenotypes.

Sajal I, Biswas S Front Genet. 2023; 14:1104727.

PMID: 36968609 PMC: 10033866. DOI: 10.3389/fgene.2023.1104727.

Bivariate logistic Bayesian LASSO for detecting rare haplotype association with two correlated phenotypes.

Yuan X, Biswas S Genet Epidemiol. 2019; 43(8):996-1017.

PMID: 31544985 PMC: 6836722. DOI: 10.1002/gepi.22258.

Comparison of haplotype-based tests for detecting gene-environment interactions with rare variants.

Papachristou C, Biswas S Brief Bioinform. 2019; 21(3):851-862.

PMID: 31329820 PMC: 7299304. DOI: 10.1093/bib/bbz031.

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