A statistical framework for cross-tissue transcriptome-wide association analysis.

Nature Genetics
Yiming HuHongyu Zhao

Abstract

Transcriptome-wide association analysis is a powerful approach to studying the genetic architecture of complex traits. A key component of this approach is to build a model to impute gene expression levels from genotypes by using samples with matched genotypes and gene expression data in a given tissue. However, it is challenging to develop robust and accurate imputation models with a limited sample size for any single tissue. Here, we first introduce a multi-task learning method to jointly impute gene expression in 44 human tissues. Compared with single-tissue methods, our approach achieved an average of 39% improvement in imputation accuracy and generated effective imputation models for an average of 120% more genes. We describe a summary-statistic-based testing framework that combines multiple single-tissue associations into a powerful metric to quantify the overall gene-trait association. We applied our method, called UTMOST (unified test for molecular signatures), to multiple genome-wide-association results and demonstrate its advantages over single-tissue strategies.

References

Jun 2, 2001·Genome Biology·H Stenmark, V M Olkkonen
Feb 7, 2004·Nature·Tao LiDarrel W Stafford
Jun 14, 2005·European Journal of Clinical Pharmacology·Hugo KohnkeMia Wadelius
Jun 19, 2007·Nature Genetics·Jonathan MarchiniPeter Donnelly
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Feb 13, 2010·Cold Spring Harbor Protocols·Ammar Al-Chalabi
Apr 24, 2010·Conservation Biology : the Journal of the Society for Conservation Biology·Benedikt R Schmidt
May 13, 2010·JAMA : the Journal of the American Medical Association·Sudha SeshadriUNKNOWN EADI1 Consortium
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Jul 17, 2010·Bioinformatics·Randall J PruimCristen J Willer
Aug 6, 2010·Nature·Tanya M TeslovichSekar Kathiresan
Aug 16, 2011·Immunobiology·Helen CrehanJohn Hardy
Jul 4, 2012·The Journal of Clinical Investigation·Alanna StrongDaniel J Rader
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Feb 15, 2013·PLoS Genetics·Xiang ZhouMatthew Stephens
Mar 29, 2013·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Richard ShervaUNKNOWN Alzheimer's Disease Genetics Consortium
May 15, 2013·PLoS Genetics·Timothée FlutreMatthew Stephens
Sep 17, 2013·Nature·Tuuli LappalainenEmmanouil T Dermitzakis
Oct 8, 2013·Nature Genetics·Cristen J WillerUNKNOWN Global Lipids Genetics Consortium
Dec 18, 2013·Human Genetics·Cong LiHongyu Zhao
Feb 20, 2015·Nature·UNKNOWN Roadmap Epigenomics ConsortiumManolis Kellis
Aug 11, 2015·Nature Genetics·Eric R GamazonHae Kyung Im
Feb 9, 2016·Nature Genetics·Alexander GusevBogdan Pasaniuc
Aug 2, 2016·Nature Genetics·Victoria HoreJonathan Marchini

❮ Previous
Next ❯

Citations

Dec 11, 2019·Genetic Epidemiology·Haoran XueUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Dec 25, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Philip D HarveyLarry J Siever
Dec 18, 2019·Acta Neuropathologica·Umber DubeCarlos Cruchaga
Feb 28, 2020·Human Reproduction·Sally MortlockGrant W Montgomery
Jun 27, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Michael W LutzOrnit Chiba-Falek
Mar 31, 2019·Nature Genetics·Michael WainbergAnshul Kundaje
Mar 3, 2020·NAR Genomics and Bioinformatics·Mingxuan CaiCan Yang
May 20, 2020·Nature Genetics·Douglas W YaoAlexander Gusev
Nov 3, 2020·PLoS Computational Biology·Wei LiuHongyu Zhao
Dec 29, 2020·Genetic Epidemiology·Nastasiya F Grinberg, Chris Wallace
Jan 14, 2021·Communications Biology·Daniel J PanyardQiongshi Lu
Jan 13, 2021·American Journal of Human Genetics·Lu LiuXiang Zhou
Jan 28, 2021·Genome Biology·Alvaro N BarbeiraHae Kyung Im
Oct 16, 2020·Nature·Alexander G BickPradeep Natarajan
Nov 17, 2020·Frontiers in Genetics·Meng SongHong-Wen Deng
Dec 23, 2020·Nature Neuroscience·Matthew J GirgentiRonald S Duman
Feb 26, 2021·PLoS Genetics·Nana LiuUNKNOWN Alzheimer’s disease Neuroimaging Initiative
May 22, 2021·PLoS Computational Biology·Arunabha MajumdarBogdan Pasaniuc
Jun 4, 2021·Genetic Epidemiology·Helian FengPeter Kraft
Jun 9, 2021·Nature Medicine·Seyedeh M ZekavatPradeep Natarajan
Jun 30, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lang WuChong Wu
Jul 25, 2021·Nature Reviews. Genetics·William R Reay, Murray J Cairns

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases

Software Mentioned

PrediXcan
CommonMind
SNPTest
STARNET
LocusZoom
GTEx
Michigan Imputation Server
TWAS
IGAP
qqman

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.