A statistical framework for cross-tissue transcriptome-wide association analysis.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
20
03
2018
accepted:
09
01
2019
pubmed:
26
2
2019
medline:
25
4
2019
entrez:
27
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30804563
doi: 10.1038/s41588-019-0345-7
pii: 10.1038/s41588-019-0345-7
pmc: PMC6788740
mid: NIHMS1052791
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
568-576Subventions
Organisme : NIA NIH HHS
ID : R01 AG054060
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000427
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NIA NIH HHS
ID : K25 AG055620
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007205
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG006781
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057508
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002373
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM059507
Pays : United States
Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : N01AG12100
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : Parkinson's UK
ID : G-0907
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL142711
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG021342
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG042437
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG041689
Pays : United States
Références
Alzheimers Dement. 2014 Jan;10(1):45-52
pubmed: 23535033
Alzheimers Dement. 2017 Jul;13(7):727-738
pubmed: 28183528
Nature. 2013 Sep 26;501(7468):506-11
pubmed: 24037378
Nat Neurosci. 2017 Aug;20(8):1052-1061
pubmed: 28628103
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Cell. 2016 Nov 17;167(5):1398-1414.e24
pubmed: 27863251
Genetics. 2017 Nov;207(3):893-902
pubmed: 28893853
Nat Genet. 2016 May;48(5):481-7
pubmed: 27019110
Nat Genet. 2011 May;43(5):436-41
pubmed: 21460841
Nat Genet. 2019 Apr;51(4):675-682
pubmed: 30926970
Am J Hum Genet. 2017 Jul 6;101(1):5-22
pubmed: 28686856
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Nat Genet. 2016 Mar;48(3):245-52
pubmed: 26854917
Neurobiol Aging. 2001 Jan-Feb;22(1):79-88
pubmed: 11164279
PLoS Genet. 2011 Aug;7(8):e1002216
pubmed: 21829393
Nature. 2012 Nov 1;491(7422):56-65
pubmed: 23128226
Ann Clin Transl Neurol. 2016 Nov 04;3(12):924-933
pubmed: 28097204
Alzheimers Dement. 2018 Feb;14(2):215-229
pubmed: 28923553
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
Am J Hum Genet. 2015 Feb 5;96(2):283-94
pubmed: 25640677
Nat Genet. 2010 Aug;42(8):698-702
pubmed: 20622878
Nat Genet. 2015 Sep;47(9):979-986
pubmed: 26192919
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Nat Genet. 2016 Sep;48(9):1094-100
pubmed: 27479908
Nat Genet. 2011 May;43(5):429-35
pubmed: 21460840
Nat Genet. 2009 Oct;41(10):1088-93
pubmed: 19734902
Genome Res. 2017 Nov;27(11):1859-1871
pubmed: 29021290
PLoS Genet. 2013;9(2):e1003264
pubmed: 23408905
PLoS Genet. 2017 Jul 24;13(7):e1006933
pubmed: 28742084
Nat Genet. 2016 Oct;48(10):1284-1287
pubmed: 27571263
Am J Hum Genet. 2017 Apr 6;100(4):605-616
pubmed: 28343628
Science. 2014 May 2;344(6183):519-23
pubmed: 24786080
Eur J Clin Pharmacol. 2005 Jul;61(5-6):381-8
pubmed: 15952022
PLoS Comput Biol. 2010 May 06;6(5):e1000770
pubmed: 20463871
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
Nat Genet. 2013 Nov;45(11):1274-1283
pubmed: 24097068
J Clin Invest. 2012 Aug;122(8):2807-16
pubmed: 22751103
Am J Hum Genet. 2017 Mar 2;100(3):473-487
pubmed: 28238358
Nat Genet. 2018 Nov;50(11):1584-1592
pubmed: 30297968
Cell. 2016 Nov 17;167(5):1415-1429.e19
pubmed: 27863252
Neuron. 2015 Feb 4;85(3):519-33
pubmed: 25619653
Twin Res Hum Genet. 2017 Apr;20(2):97-107
pubmed: 28193307
Science. 2016 Aug 19;353(6301):827-30
pubmed: 27540175
Mol Psychiatry. 2015 Feb;20(2):183-92
pubmed: 25644384
Genome Res. 2017 Nov;27(11):1872-1884
pubmed: 29021289
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Nature. 2017 Oct 11;550(7675):204-213
pubmed: 29022597
Nat Neurosci. 2016 Nov;19(11):1442-1453
pubmed: 27668389
Neurobiol Aging. 2013 Apr;34(4):1105-15
pubmed: 23063647
Nature. 2004 Feb 5;427(6974):541-4
pubmed: 14765195
Cell. 2017 Jun 15;169(7):1177-1186
pubmed: 28622505
Gene Ther. 2012 Jul;19(7):724-33
pubmed: 21918553
Hum Mol Genet. 2014 May 15;23(10):2780-90
pubmed: 24381306
Nature. 2010 Aug 5;466(7307):707-13
pubmed: 20686565
Nat Genet. 2015 Nov;47(11):1228-35
pubmed: 26414678
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
JAMA. 2010 May 12;303(18):1832-40
pubmed: 20460622
Immunobiology. 2012 Feb;217(2):244-50
pubmed: 21840620
PLoS Genet. 2013 Jun;9(6):e1003491
pubmed: 23785294
PLoS Genet. 2013 May;9(5):e1003486
pubmed: 23671422
Nat Genet. 2015 Dec;47(12):1457-1464
pubmed: 26502338
Genome Res. 2017 Nov;27(11):1843-1858
pubmed: 29021288
Hum Genet. 2014 May;133(5):639-50
pubmed: 24337655
Nat Genet. 2017 Mar;49(3):325-331
pubmed: 28092683
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Nat Genet. 2017 Feb;49(2):256-261
pubmed: 28067908
Nature. 2010 Aug 5;466(7307):714-9
pubmed: 20686566
BMC Bioinformatics. 2018 Mar 9;19(1):95
pubmed: 29523079
Bioinformatics. 2017 Jul 15;33(14):i67-i74
pubmed: 28881962
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Neurobiol Aging. 2016 Feb;38:141-150
pubmed: 26827652
Nat Genet. 2018 Apr;50(4):621-629
pubmed: 29632380
PLoS Genet. 2017 Jun 9;13(6):e1006836
pubmed: 28598966
Nat Genet. 2007 Jul;39(7):906-13
pubmed: 17572673
Nat Genet. 2009 Oct;41(10):1094-9
pubmed: 19734903
PLoS Genet. 2010 Apr 01;6(4):e1000888
pubmed: 20369019
J Am Stat Assoc. 2017;112(519):1032-1046
pubmed: 29375169
Am J Hum Genet. 2016 Dec 1;99(6):1245-1260
pubmed: 27866706
PLoS Genet. 2017 Mar 31;13(3):e1006690
pubmed: 28362817