Heritability estimation and differential analysis of count data with generalized linear mixed models in genomic sequencing studies

Bioinformatics
Shiquan SunXiang Zhou

Abstract

Genomic sequencing studies, including RNA sequencing and bisulfite sequencing studies, are becoming increasingly common and increasingly large. Large genomic sequencing studies open doors for accurate molecular trait heritability estimation and powerful differential analysis. Heritability estimation and differential analysis in sequencing studies requires the development of statistical methods that can properly account for the count nature of the sequencing data and that are computationally efficient for large datasets. Here, we develop such a method, PQLseq (Penalized Quasi-Likelihood for sequencing count data), to enable effective and efficient heritability estimation and differential analysis using the generalized linear mixed model framework. With extensive simulations and comparisons to previous methods, we show that PQLseq is the only method currently available that can produce unbiased heritability estimates for sequencing count data. In addition, we show that PQLseq is well suited for differential analysis in large sequencing studies, providing calibrated type I error control and more power compared to the standard linear mixed model methods. Finally, we apply PQLseq to perform gene expression heritability estimation an...Continue Reading

References

May 23, 1998·American Journal of Human Genetics·L Almasy, J Blangero
Jan 13, 2000·American Journal of Human Genetics·G R AbecasisW O Cookson
Oct 30, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marquis P VawterWilliam E Bunney
Mar 6, 2008·Nature Reviews. Genetics·Peter M VisscherNaomi R Wray
Mar 18, 2008·Nature·Valur EmilssonKari Stefansson
Dec 8, 2009·Biostatistics·Youyi FongJon Wakefield
Mar 12, 2010·Nature·Joseph K PickrellJonathan K Pritchard
Jun 22, 2010·Nature Genetics·Jian YangPeter M Visscher
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Aug 4, 2011·Bioinformatics·Yi-Hui ZhouFred A Wright
Sep 6, 2011·Nature Methods·Christoph LippertDavid Heckerman
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Feb 15, 2013·PLoS Genetics·Xiang ZhouMatthew Stephens
May 28, 2013·G3 : Genes - Genomes - Genetics·Anna Marie HolandHenrik Jensen
Jun 19, 2013·Nature Reviews. Genetics·Naomi R WrayPeter M Visscher
Sep 17, 2013·Nature·Tuuli LappalainenEmmanouil T Dermitzakis
Nov 19, 2013·Nature Reviews. Genetics·Gustavo de los Campos, Daniel A Sorensen
Dec 10, 2013·G3 : Genes - Genomes - Genetics·Bernardo LemosColin D Meiklejohn
Feb 26, 2014·Genome Biology·Deqiang SunWei Li
Apr 15, 2014·Nature Genetics·Fred A WrightDorret I Boomsma
Jun 3, 2014·Genome Biology·Allan F McRaeGrant W Montgomery
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
May 6, 2015·PLoS Genetics·Gustavo de Los CamposDaniel Gianola
Jan 28, 2016·Genome Biology·Ana ConesaAli Mortazavi
Mar 5, 2016·Human Molecular Genetics·Darren A CusanovichCarole Ober
Jun 30, 2016·Nature Communications·Laura J ScottStephen C J Parker
Jan 5, 2017·BMC Bioinformatics·Xinyan ZhangNengjun Yi
Apr 4, 2017·Nucleic Acids Research·Shiquan SunXiang Zhou

❮ Previous
Next ❯

Citations

Aug 19, 2020·Briefings in Bioinformatics·Denis Awany, Emile R Chimusa
May 2, 2020·Animal Cognition·Marina M WatowichNoah Snyder-Mackler
Jul 9, 2020·Computational and Structural Biotechnology Journal·Huanhuan Zhu, Xiang Zhou
Jun 19, 2021·Computational and Structural Biotechnology Journal·Ping ZengXiang Zhou
Jul 11, 2021·Trends in Genetics : TIG·Ying Ma, Xiang Zhou

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.