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

Human Heredity
Ananda S DattaSwati Biswas

Abstract

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. 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. 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...Continue Reading

References

May 29, 2000·American Journal of Human Genetics·E R MartinN L Kaplan
Jan 16, 2002·American Journal of Human Genetics·Daniel J SchaidGregory A Poland
Oct 18, 2002·Genetic Epidemiology·Richard W Morris, Norman L Kaplan
Nov 16, 2004·Genetic Epidemiology·Daniel J Schaid
Oct 15, 2005·Human Heredity·Suzanne M LealBertram Müller-Myhsok
Jul 17, 2009·Annals of Human Genetics·Anatoly V KirichenkoTatiana I Axenovich
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
Oct 23, 2009·Genetic Epidemiology·Xiaofeng ZhuRobert C Elston
Dec 19, 2009·BMC Proceedings·L Adrienne CupplesUNKNOWN Framingham Heart Study Investigators
Jul 20, 2011·Genetic Epidemiology·Saonli Basu, Wei Pan
Dec 14, 2011·Genetic Epidemiology·Carmen DeringAndreas Ziegler
Jun 19, 2012·Genetic Epidemiology·Wan-Yu LinNianjun Liu
Jan 24, 2013·PloS One·Gourab DeNan Laird
Mar 28, 2013·European Journal of Human Genetics : EJHG·Miao HanShili Lin
Jun 12, 2013·Nature Reviews. Genetics·David B GoldsteinShamil Sunyaev
Nov 26, 2013·Genetic Epidemiology·Swati BiswasShili Lin
Dec 19, 2014·BMC Proceedings·Swati Biswas, Charalampos Papachristou
Jan 18, 2015·Briefings in Bioinformatics·Meng Wang, Shili Lin
Sep 5, 2015·Briefings in Bioinformatics·Ananda S Datta, Swati Biswas
Jul 12, 2016·Nature·Christian FuchsbergerMark I McCarthy
Dec 17, 2016·BMC Proceedings·Ananda S DattaSwati Biswas

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Citations

Jul 23, 2019·Briefings in Bioinformatics·Charalampos Papachristou, Swati Biswas

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