Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
27 Oct 2023
27 Oct 2023
Historique:
pubmed:
14
11
2023
medline:
14
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. Here, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34K conditionally distinct expression quantitative trait locus (eQTL) signals in 18K genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared to primary signals, non-primary signals had lower effect sizes, lower minor allele frequencies, and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTL with conditionally distinct genome-wide association study signals for 28 cardiometabolic traits identified 3,605 eQTL signals for 1,861 genes. Inclusion of non-primary eQTL signals increased colocalized signals by 46%. Among 30 genes with ≥2 pairs of colocalized signals, 21 showed a mediating gene dosage effect on the trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.
Identifiants
pubmed: 37961277
doi: 10.1101/2023.10.26.563798
pmc: PMC10634839
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : Intramural NIH HHS
ID : ZIA HG000024
Pays : United States
Organisme : NIDDK NIH HHS
ID : UM1 DK105554
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA006227
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101782
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101810
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090936
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062370
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL129982
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL154730
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090951
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101820
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH101819
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010505
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK072193
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL170604
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK105554
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007092
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101825
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090948
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090941
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK132775
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101822
Pays : United States
Organisme : CCR NIH HHS
ID : HHSN261200800001C
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK105561
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH090937
Pays : United States
Organisme : NIDDK NIH HHS
ID : UM1 DK126185
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL146121
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201000029C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101814
Pays : United States
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing interests.
Références
Nat Genet. 2016 May;48(5):481-7
pubmed: 27019110
Nature. 2020 Jun;582(7811):240-245
pubmed: 32499647
PLoS Genet. 2021 Oct 26;17(10):e1009865
pubmed: 34699533
Nat Genet. 2022 Feb;54(2):161-169
pubmed: 35058635
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Nat Genet. 2021 Sep;53(9):1300-1310
pubmed: 34475573
Nat Genet. 2012 Oct;44(10):1084-9
pubmed: 22941192
Mol Metab. 2022 Sep;63:101543
pubmed: 35811051
Nat Genet. 2015 Jan;47(1):88-91
pubmed: 25436857
Diabetes. 1998 Jul;47(7):1135-44
pubmed: 9648839
Nat Genet. 2016 Oct;48(10):1279-83
pubmed: 27548312
PLoS Genet. 2021 Apr 19;17(4):e1009455
pubmed: 33872308
PLoS Genet. 2021 Sep 29;17(9):e1009440
pubmed: 34587156
Endocr Rev. 2008 Dec;29(7):777-822
pubmed: 18971485
Am J Hum Genet. 2017 May 4;100(5):789-802
pubmed: 28475861
Life Sci. 2021 Oct 15;283:119857
pubmed: 34339715
Hum Mol Genet. 2018 Oct 15;27(20):3641-3649
pubmed: 30124842
Elife. 2022 Dec 14;11:
pubmed: 36515579
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
PLoS Genet. 2020 Apr 20;16(4):e1008720
pubmed: 32310995
PLoS Genet. 2014 Sep 11;10(9):e1004633
pubmed: 25211022
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Arterioscler Thromb Vasc Biol. 2018 Aug;38(8):e137-e144
pubmed: 30354196
Obes Facts. 2008;1(4):184-9
pubmed: 20054179
Hum Mol Genet. 2017 Apr 15;26(8):1444-1451
pubmed: 28165122
Aging Cell. 2007 Aug;6(4):515-23
pubmed: 17559502
Nat Commun. 2022 Jun 30;13(1):3771
pubmed: 35773277
Am J Hum Genet. 2016 Sep 1;99(3):567-579
pubmed: 27588447
Science. 2020 Sep 11;369(6509):1318-1330
pubmed: 32913098
Genetics. 2023 Jan 12;223(1):
pubmed: 36321965
Am J Hum Genet. 2011 Jan 7;88(1):76-82
pubmed: 21167468
Trends Genet. 2021 Feb;37(2):109-124
pubmed: 32912663
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Nature. 2017 Oct 11;550(7675):204-213
pubmed: 29022597
Nature. 2021 Dec;600(7890):675-679
pubmed: 34887591
Am J Hum Genet. 2018 May 3;102(5):717-730
pubmed: 29727686
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Nat Protoc. 2012 Feb 16;7(3):500-7
pubmed: 22343431
Genetics. 2019 Jul;212(3):905-918
pubmed: 31123039
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Nat Genet. 2019 Feb;51(2):343-353
pubmed: 30692680
Nature. 2013 Sep 26;501(7468):506-11
pubmed: 24037378
J Lipid Res. 2017 Mar;58(3):481-493
pubmed: 28119442
Nat Genet. 2022 Dec;54(12):1803-1815
pubmed: 36474045
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Methods Mol Biol. 2017;1566:77-85
pubmed: 28244042
Nat Genet. 2018 Nov;50(11):1505-1513
pubmed: 30297969
IUBMB Life. 2020 Aug;72(8):1546-1559
pubmed: 32233118
BMC Bioinformatics. 2015 Jul 19;16:224
pubmed: 26187896
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Philos Trans R Soc Lond B Biol Sci. 2013 May 06;368(1620):20120362
pubmed: 23650636
Nat Genet. 2021 Jun;53(6):840-860
pubmed: 34059833
Nat Genet. 2023 Nov;55(11):1866-1875
pubmed: 37857933
Am J Hum Genet. 2018 Jun 7;102(6):1169-1184
pubmed: 29805045
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Nat Genet. 2018 Oct;50(10):1412-1425
pubmed: 30224653
Nat Commun. 2016 Jun 29;7:11764
pubmed: 27353450
Nat Genet. 2010 Oct;42(10):902-5
pubmed: 20835236
Am J Hum Genet. 2019 Oct 3;105(4):773-787
pubmed: 31564431
Hum Mol Genet. 2019 Dec 15;28(24):4161-4172
pubmed: 31691812
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Redox Biol. 2017 Aug;12:806-813
pubmed: 28441629
Bioinformatics. 2016 May 15;32(10):1479-85
pubmed: 26708335
Diabetes. 2023 Nov 1;72(11):1707-1718
pubmed: 37647564
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Int J Biochem Cell Biol. 2012 Dec;44(12):2278-87
pubmed: 22982762
PLoS Genet. 2010 Apr 01;6(4):e1000888
pubmed: 20369019
Am J Hum Genet. 2017 Mar 2;100(3):428-443
pubmed: 28257690
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Hum Mol Genet. 2019 Jan 1;28(1):166-174
pubmed: 30239722
N Engl J Med. 1996 Feb 1;334(5):292-5
pubmed: 8532024
Diabetologia. 2013 Aug;56(8):1792-801
pubmed: 23666167
Int J Obes (Lond). 2022 Aug;46(8):1478-1486
pubmed: 35589964
Am J Hum Genet. 2022 Feb 3;109(2):223-239
pubmed: 35085493
Nat Commun. 2017 May 18;8:15452
pubmed: 28516912