MultiPhen: joint model of multiple phenotypes can increase discovery in GWAS.

PloS One
Paul F O'ReillyLachlan J M Coin

Abstract

The genome-wide association study (GWAS) approach has discovered hundreds of genetic variants associated with diseases and quantitative traits. However, despite clinical overlap and statistical correlation between many phenotypes, GWAS are generally performed one-phenotype-at-a-time. Here we compare the performance of modelling multiple phenotypes jointly with that of the standard univariate approach. We introduce a new method and software, MultiPhen, that models multiple phenotypes simultaneously in a fast and interpretable way. By performing ordinal regression, MultiPhen tests the linear combination of phenotypes most associated with the genotypes at each SNP, and thus potentially captures effects hidden to single phenotype GWAS. We demonstrate via simulation that this approach provides a dramatic increase in power in many scenarios. There is a boost in power for variants that affect multiple phenotypes and for those that affect only one phenotype. While other multivariate methods have similar power gains, we describe several benefits of MultiPhen over these. In particular, we demonstrate that other multivariate methods that assume the genotypes are normally distributed, such as canonical correlation analysis (CCA) and MANOVA...Continue Reading

References

Oct 1, 1980·Biochemical Society Transactions·J Shepherd
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Jun 19, 2007·Nature Genetics·Jonathan MarchiniPeter Donnelly
Nov 21, 2008·Bioinformatics·Manuel A R Ferreira, Shaun M Purcell
May 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lucia A HindorffTeri A Manolio
Aug 27, 2009·European Journal of Human Genetics : EJHG·Sarah Elizabeth Medland, Michael Churton Neale
Dec 29, 2009·Nature Genetics·Thomas IlligKarsten Suhre
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Oct 12, 2010·Nature Genetics·Elizabeth K SpeliotesRuth J F Loos
Aug 20, 2011·PLoS Genetics·Chris CotsapasUNKNOWN FOCiS Network of Consortia
Sep 13, 2011·Nature·UNKNOWN International Consortium for Blood Pressure Genome-Wide Association StudiesToby Johnson
Dec 6, 2011·Nature·Christian GiegerNicole Soranzo

❮ Previous
Next ❯

Citations

Apr 26, 2014·PloS One·Tessel E GaleslootSita H Vermeulen
Mar 19, 2014·Trends in Genetics : TIG·Matthew R RobinsonPeter M Visscher
Dec 7, 2013·Behavior Genetics·Gitta Lubke, Daniel McArtor
Jan 30, 2013·PLoS Genetics·Sophie van der SluisConor V Dolan
Dec 18, 2013·Development and Psychopathology·Robert Plomin, Michael A Simpson
Feb 16, 2016·Nature Reviews. Genetics·William S BushDana C Crawford
Sep 28, 2015·Behavior Genetics·Malgorzata LagiszShinichi Nakagawa
Feb 24, 2016·Nature Genetics·Andrew DahlJonathan Marchini
Jan 20, 2016·Genetic Epidemiology·Baolin Wu, James S Pankow
May 3, 2016·Stat : the ISI's Journal for Rapid Dissemination of Statistics Research·Yubin SungSanjeena Subedi
Mar 5, 2016·American Journal of Human Genetics·K Alaine BroadawayMichael P Epstein
Mar 1, 2016·American Journal of Human Genetics·Daniel GreeneErnest Turro
Dec 8, 2015·Genetic Epidemiology·Debashree RaySaonli Basu
Mar 19, 2016·Annals of Human Genetics·Zhenchuan WangShuanglin Zhang
Dec 17, 2014·American Journal of Human Genetics·Xiaofeng ZhuSusan Redline
Apr 8, 2014·NeuroImage·Yiwei ZhangUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jun 7, 2014·Biochimica Et Biophysica Acta·Harish DharuriKo Willems van Dijk
Jun 27, 2015·BMC Medical Genomics·Akram AlyassDavid Meyre
Jun 25, 2015·Nature Communications·Kaustubh AdhikariAndrés Ruiz-Linares
Mar 24, 2015·Frontiers in Bioengineering and Biotechnology·Arnald AlonsoAntonio Julià
Nov 29, 2014·Bioinformatics·Sophie Van der SluisMiao-Xin Li
Nov 5, 2014·Frontiers in Genetics·Weiqiang WangZuoheng Wang
Oct 21, 2014·PLoS Computational Biology·Jose A SeoaneTom R Gaunt
Oct 21, 2015·PloS One·Xiaobo GuoHeping Zhang
Jun 2, 2016·Pharmacogenomics·Matthew T OetjensDana C Crawford

❮ Previous
Next ❯

Software Mentioned

IMPUTE
CCA
MultiPhen
Java
R

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.

Related Papers

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics
Elaine K GreenNick Craddock
European Journal of Human Genetics : EJHG
Jian YangGIANT Consortium
© 2021 Meta ULC. All rights reserved