Fast genome-wide pedigree quantitative trait loci analysis using MENDEL

The linkage era left a rich legacy of pedigree samples that can be used for modern genome-wide association sequencing (GWAS) or next-generation sequencing (NGS) studies. Family designs are naturally equipped to detect rare variants, control for population stratification, and facilitate the study of...

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Main Authors:	Zhou, Hua, Zhou, Jin, Sobel, Eric M, Lange, Kenneth
Format:	Online
Language:	English
Published:	BioMed Central 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143629/

id	pubmed-4143629
recordtype	oai_dc
spelling	pubmed-41436292014-09-02 Fast genome-wide pedigree quantitative trait loci analysis using MENDEL Zhou, Hua Zhou, Jin Sobel, Eric M Lange, Kenneth Proceedings The linkage era left a rich legacy of pedigree samples that can be used for modern genome-wide association sequencing (GWAS) or next-generation sequencing (NGS) studies. Family designs are naturally equipped to detect rare variants, control for population stratification, and facilitate the study of parent-of-origin effects. Unfortunately, pedigree likelihoods are notoriously hard to compute, and current software for association mapping in pedigrees is prohibitively slow in processing dense marker maps. In a recent release of the comprehensive genetic analysis software MENDEL, we implemented an ultra-fast score test for association mapping with pedigree-based GWAS or NGS study data. Our implementation (a) works for random sample data, pedigree data, or a mix of both;(b) allows for covariate adjustment, including correction for population stratification;(c) accommodates both univariate and multivariate quantitative traits; and (d) allows missing values in multivariate traits. In this paper, we assess the capabilities of MENDEL on the Genetic Analysis Workshop 18 sequencing data. For instance, when jointly testing the 4 longitudinally measured diastolic blood pressure traits, it takes MENDEL less than 51 minutes on a standard laptop computer to read, quality check, and analyze a data set with 959 individuals and 8.3 million single-nucleotide polymorphisms (SNPs). Our analysis reveals association of one SNP in the q32.2 region of chromosome 1. MENDEL is freely available on http://www.genetics.ucla.edu/software. BioMed Central 2014-06-17 /pmc/articles/PMC4143629/ /pubmed/25519348 http://dx.doi.org/10.1186/1753-6561-8-S1-S93 Text en Copyright © 2014 Zhou et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhou, Hua Zhou, Jin Sobel, Eric M Lange, Kenneth
spellingShingle	Zhou, Hua Zhou, Jin Sobel, Eric M Lange, Kenneth Fast genome-wide pedigree quantitative trait loci analysis using MENDEL
author_facet	Zhou, Hua Zhou, Jin Sobel, Eric M Lange, Kenneth
author_sort	Zhou, Hua
title	Fast genome-wide pedigree quantitative trait loci analysis using MENDEL
title_short	Fast genome-wide pedigree quantitative trait loci analysis using MENDEL
title_full	Fast genome-wide pedigree quantitative trait loci analysis using MENDEL
title_fullStr	Fast genome-wide pedigree quantitative trait loci analysis using MENDEL
title_full_unstemmed	Fast genome-wide pedigree quantitative trait loci analysis using MENDEL
title_sort	fast genome-wide pedigree quantitative trait loci analysis using mendel
description	The linkage era left a rich legacy of pedigree samples that can be used for modern genome-wide association sequencing (GWAS) or next-generation sequencing (NGS) studies. Family designs are naturally equipped to detect rare variants, control for population stratification, and facilitate the study of parent-of-origin effects. Unfortunately, pedigree likelihoods are notoriously hard to compute, and current software for association mapping in pedigrees is prohibitively slow in processing dense marker maps. In a recent release of the comprehensive genetic analysis software MENDEL, we implemented an ultra-fast score test for association mapping with pedigree-based GWAS or NGS study data. Our implementation (a) works for random sample data, pedigree data, or a mix of both;(b) allows for covariate adjustment, including correction for population stratification;(c) accommodates both univariate and multivariate quantitative traits; and (d) allows missing values in multivariate traits. In this paper, we assess the capabilities of MENDEL on the Genetic Analysis Workshop 18 sequencing data. For instance, when jointly testing the 4 longitudinally measured diastolic blood pressure traits, it takes MENDEL less than 51 minutes on a standard laptop computer to read, quality check, and analyze a data set with 959 individuals and 8.3 million single-nucleotide polymorphisms (SNPs). Our analysis reveals association of one SNP in the q32.2 region of chromosome 1. MENDEL is freely available on http://www.genetics.ucla.edu/software.
publisher	BioMed Central
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143629/
_version_	1613127362827780096

Fast genome-wide pedigree quantitative trait loci analysis using MENDEL

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