Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.
Case-Control Studies
Cohort Studies
Computer Simulation
Data Interpretation, Statistical
Gene Expression Regulation
Gene-Environment Interaction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Models, Genetic
Pancreatic Neoplasms
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Quantitative Trait Loci
/ genetics
Smoking
/ genetics
PrediXCan
data-adaptive association testing
eQTL
gene-by-environment interaction
multiple functional weights
Journal
Genetic epidemiology
ISSN: 1098-2272
Titre abrégé: Genet Epidemiol
Pays: United States
ID NLM: 8411723
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
03
02
2020
revised:
14
07
2020
accepted:
30
07
2020
pubmed:
12
8
2020
medline:
26
5
2021
entrez:
12
8
2020
Statut:
ppublish
Résumé
It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes, TRIP10 and KDM3A, were identified. The aGEw test is implemented in an R package aGE.
Identifiants
pubmed: 32779232
doi: 10.1002/gepi.22348
pmc: PMC7657998
mid: NIHMS1641697
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
880-892Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL126032
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA169122
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA154823
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL116720
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Genetics. 2014 Aug;197(4):1081-95
pubmed: 24831820
Nat Rev Genet. 2005 Apr;6(4):287-98
pubmed: 15803198
Stat Sci. 2009 Nov;24(4):398-413
pubmed: 20711421
Gastroenterology. 1991 May;100(5 Pt 1):1392-6
pubmed: 2013384
PLoS Genet. 2018 Jan 29;14(1):e1007186
pubmed: 29377896
Cancer Lett. 2010 Feb 1;288(1):116-23
pubmed: 19631450
Front Genet. 2013 May 31;4:103
pubmed: 23755072
PLoS One. 2019 Aug 8;14(8):e0220827
pubmed: 31393916
Genetics. 2017 Nov;207(3):893-902
pubmed: 28893853
Am J Epidemiol. 2017 Oct 1;186(7):778-786
pubmed: 28978190
Nat Genet. 2014 Sep;46(9):994-1000
pubmed: 25086665
Nat Genet. 2016 Mar;48(3):245-52
pubmed: 26854917
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
Prog Neurobiol. 2016 Jan;136:1-27
pubmed: 26510407
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
Nature. 2010 Oct 28;467(7319):1061-73
pubmed: 20981092
Hum Mol Genet. 2020 Feb 1;29(3):515-526
pubmed: 31919517
Epigenomics. 2016 Jun;8(6):831-42
pubmed: 27337224
Nat Commun. 2018 Feb 8;9(1):556
pubmed: 29422604
Bioinformatics. 2017 Jan 1;33(1):64-71
pubmed: 27592708
Gastroenterology. 2019 Dec;157(6):1646-1659.e11
pubmed: 31442435
Respir Res. 2014 Sep 24;15:94
pubmed: 25248511
Nat Genet. 2010 Mar;42(3):224-8
pubmed: 20101243
Biostatistics. 2017 Jan;18(1):119-131
pubmed: 27474101
Genet Epidemiol. 2013 Nov;37(7):643-57
pubmed: 24123198
Nat Genet. 2015 Aug;47(8):911-6
pubmed: 26098869
Stat Med. 2019 Mar 30;38(7):1230-1244
pubmed: 30460711
Nat Genet. 2009 Sep;41(9):986-90
pubmed: 19648918
J Child Psychol Psychiatry. 2013 Oct;54(10):1109-19
pubmed: 23909413
Nat Genet. 2019 Apr;51(4):592-599
pubmed: 30926968
Nat Genet. 2011 Dec 11;44(1):62-6
pubmed: 22158540
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Carcinogenesis. 2014 May;35(5):1039-45
pubmed: 24419231
Int J Epidemiol. 1984 Sep;13(3):356-65
pubmed: 6386716
Genet Epidemiol. 2010 May;34(4):364-72
pubmed: 20091798
Genet Epidemiol. 2020 Jan;44(1):104-116
pubmed: 31830326
Genetics. 2018 Jul;209(3):699-709
pubmed: 29728367
PLoS Genet. 2019 Jan 22;15(1):e1007889
pubmed: 30668570
PLoS Genet. 2019 Apr 29;15(4):e1008081
pubmed: 31034468
Am J Hum Genet. 2007 Feb;80(2):353-60
pubmed: 17236140
Curr Environ Health Rep. 2017 Jun;4(2):192-199
pubmed: 28417442
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Hum Hered. 2014;78(2):81-90
pubmed: 25060534
Biometrics. 2016 Mar;72(1):156-64
pubmed: 26229047
Am J Hum Genet. 2013 May 2;92(5):667-80
pubmed: 23643380
PLoS One. 2010 Jul 29;5(7):e11824
pubmed: 20686608
Front Genet. 2013 May 31;3:228
pubmed: 23755064
Science. 2004 Oct 22;306(5696):636-40
pubmed: 15499007
Nat Rev Genet. 2015 Apr;16(4):197-212
pubmed: 25707927
J Thyroid Res. 2016;2016:2454989
pubmed: 27123358
Trends Genet. 2013 Aug;29(8):479-87
pubmed: 23769209
PLoS Genet. 2010 Apr 01;6(4):e1000888
pubmed: 20369019
Clin Epigenetics. 2019 Dec 4;11(1):183
pubmed: 31801625