PMID- 30804563
OWN - NLM
STAT- MEDLINE
DCOM- 20190424
LR  - 20231014
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 51
IP  - 3
DP  - 2019 Mar
TI  - A statistical framework for cross-tissue transcriptome-wide association analysis.
PG  - 568-576
LID - 10.1038/s41588-019-0345-7 [doi]
AB  - 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.
FAU - Hu, Yiming
AU  - Hu Y
AUID- ORCID: 0000-0002-0988-1030
AD  - Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
FAU - Li, Mo
AU  - Li M
AD  - Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
FAU - Lu, Qiongshi
AU  - Lu Q
AUID- ORCID: 0000-0002-4514-0969
AD  - Department of Biostatistics and Medical Informatics, University of 
      Wisconsin-Madison, Madison, WI, USA.
FAU - Weng, Haoyi
AU  - Weng H
AD  - Division of Biostatistics, The Jockey Club School of Public Health and Primary 
      Care, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
FAU - Wang, Jiawei
AU  - Wang J
AD  - Program of Computational Biology and Bioinformatics, Yale University, New Haven, 
      CT, USA.
FAU - Zekavat, Seyedeh M
AU  - Zekavat SM
AUID- ORCID: 0000-0003-4026-8944
AD  - Yale School of Medicine, New Haven, CT, USA.
AD  - Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
FAU - Yu, Zhaolong
AU  - Yu Z
AD  - Program of Computational Biology and Bioinformatics, Yale University, New Haven, 
      CT, USA.
FAU - Li, Boyang
AU  - Li B
AUID- ORCID: 0000-0003-2808-9986
AD  - Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
FAU - Gu, Jianlei
AU  - Gu J
AD  - SJTU-Yale Joint Center for Biostatistics, Department of Bioinformatics and 
      Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiaotong 
      University, Shanghai, China.
FAU - Muchnik, Sydney
AU  - Muchnik S
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
FAU - Shi, Yu
AU  - Shi Y
AD  - Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
FAU - Kunkle, Brian W
AU  - Kunkle BW
AUID- ORCID: 0000-0002-9515-5157
AD  - John P. Hussman Institute for Human Genomics, University of Miami Miller School 
      of Medicine, Miami, FL, USA.
FAU - Mukherjee, Shubhabrata
AU  - Mukherjee S
AUID- ORCID: 0000-0003-2522-2884
AD  - Department of Medicine, University of Washington, Seattle, WA, USA.
FAU - Natarajan, Pradeep
AU  - Natarajan P
AUID- ORCID: 0000-0001-8402-7435
AD  - Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 
      Cambridge, MA, USA.
AD  - Department of Medicine, Harvard Medical School, Boston, MA, USA.
AD  - Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
FAU - Naj, Adam
AU  - Naj A
AD  - Center for Clinical Epidemiology and Biostatistic, and the Department of 
      Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Kuzma, Amanda
AU  - Kuzma A
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Zhao, Yi
AU  - Zhao Y
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA, USA.
FAU - Crane, Paul K
AU  - Crane PK
AD  - Department of Medicine, University of Washington, Seattle, WA, USA.
CN  - Alzheimer's Disease Genetics Consortium,
FAU - Lu, Hui
AU  - Lu H
AD  - SJTU-Yale Joint Center for Biostatistics, Department of Bioinformatics and 
      Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiaotong 
      University, Shanghai, China.
FAU - Zhao, Hongyu
AU  - Zhao H
AUID- ORCID: 0000-0003-1195-9607
AD  - Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA. 
      hongyu.zhao@yale.edu.
AD  - Program of Computational Biology and Bioinformatics, Yale University, New Haven, 
      CT, USA. hongyu.zhao@yale.edu.
AD  - SJTU-Yale Joint Center for Biostatistics, Department of Bioinformatics and 
      Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiaotong 
      University, Shanghai, China. hongyu.zhao@yale.edu.
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA. 
      hongyu.zhao@yale.edu.
LA  - eng
GR  - R01 AG054060/AG/NIA NIH HHS/United States
GR  - UL1 TR000427/TR/NCATS NIH HHS/United States
GR  - U24 AG021886/AG/NIA NIH HHS/United States
GR  - U01 AG032984/AG/NIA NIH HHS/United States
GR  - K25 AG055620/AG/NIA NIH HHS/United States
GR  - R01 AG033193/AG/NIA NIH HHS/United States
GR  - T32 GM007205/GM/NIGMS NIH HHS/United States
GR  - U01 AG006781/AG/NIA NIH HHS/United States
GR  - R01 AG057508/AG/NIA NIH HHS/United States
GR  - UL1 TR002373/TR/NCATS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - G0701075/MRC_/Medical Research Council/United Kingdom
GR  - G0901254/MRC_/Medical Research Council/United Kingdom
GR  - R01 GM059507/GM/NIGMS NIH HHS/United States
GR  - MR/K01417X/1/MRC_/Medical Research Council/United Kingdom
GR  - N01AG12100/AG/NIA NIH HHS/United States
GR  - U01 AG016976/AG/NIA NIH HHS/United States
GR  - G-0907/PUK_/Parkinson's UK/United Kingdom
GR  - R01 HL105756/HL/NHLBI NIH HHS/United States
GR  - MR/N026004/1/MRC_/Medical Research Council/United Kingdom
GR  - R01 HL142711/HL/NHLBI NIH HHS/United States
GR  - P30 AG021342/AG/NIA NIH HHS/United States
GR  - R01 AG042437/AG/NIA NIH HHS/United States
GR  - U24 AG041689/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190225
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
SB  - IM
MH  - Gene Expression/genetics
MH  - Gene Expression Profiling/methods
MH  - Genome-Wide Association Study/methods
MH  - Genotype
MH  - Humans
MH  - Models, Genetic
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Transcriptome/*genetics
PMC - PMC6788740
MID - NIHMS1052791
EDAT- 2019/02/26 06:00
MHDA- 2019/04/25 06:00
PMCR- 2019/10/11
CRDT- 2019/02/27 06:00
PHST- 2018/03/20 00:00 [received]
PHST- 2019/01/09 00:00 [accepted]
PHST- 2019/02/26 06:00 [pubmed]
PHST- 2019/04/25 06:00 [medline]
PHST- 2019/02/27 06:00 [entrez]
PHST- 2019/10/11 00:00 [pmc-release]
AID - 10.1038/s41588-019-0345-7 [pii]
AID - 10.1038/s41588-019-0345-7 [doi]
PST - ppublish
SO  - Nat Genet. 2019 Mar;51(3):568-576. doi: 10.1038/s41588-019-0345-7. Epub 2019 Feb 
      25.