Genetic architecture of microRNA expression and its link to complex diseases in the Japanese population.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
04 06 2022
04 06 2022
Historique:
received:
15
07
2021
revised:
04
10
2021
accepted:
23
11
2021
pubmed:
18
12
2021
medline:
9
6
2022
entrez:
17
12
2021
Statut:
ppublish
Résumé
Understanding the genetic effects on non-coding RNA (ncRNA) expression facilitates functional characterization of disease-associated genetic loci. Among several classes of ncRNAs, microRNAs (miRNAs) are key post-transcriptional gene regulators. Despite its biological importance, previous studies on the genetic architecture of miRNA expression focused mostly on the European individuals, underrepresented in other populations. Here, we mapped miRNA expression quantitative trait loci (miRNA-eQTL) for 343 miRNAs in 141 Japanese using small RNA sequencing and whole-genome sequencing, identifying 1275 cis-miRNA-eQTL variants for 40 miRNAs (false discovery rate < 0.2). Of these, 25 miRNAs having eQTL were unreported in the European studies, including 5 miRNAs with their lead variant monomorphic in the European populations, which demonstrates the value of miRNA-eQTL analysis in diverse ancestral populations. MiRNAs with eQTL effect showed allele-specific expression (ASE; e.g. miR-146a-3p), and ASE analysis further detected cis-regulatory variants not captured by the conventional miRNA-eQTL mapping (e.g. miR-933). We identified a copy number variation associated with miRNA expression (e.g. miR-570-3p, P = 7.2 × 10-6), which contributes to a more comprehensive landscape of miRNA-eQTLs. To elucidate a post-transcriptional modification in miRNAs, we created a catalog of miRNA-editing sites, including 10 canonical and 6 non-canonical sites. Finally, by integrating the miRNA-eQTLs and Japanese genome-wide association studies of 25 complex traits (mean n = 192 833), we conducted a transcriptome-wide association study, identifying miR-1908-5p as a potential mediator for adult height, colorectal cancer and type 2 diabetes (P < 9.1 × 10-5). Our study broadens the population diversity in ncRNA-eQTL studies and contributes to functional annotation of disease-associated loci found in non-European populations.
Identifiants
pubmed: 34919704
pii: 6464692
doi: 10.1093/hmg/ddab361
pmc: PMC9169454
doi:
Substances chimiques
MicroRNAs
0
RNA, Untranslated
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1806-1820Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Références
Genome Res. 2010 Feb;20(2):257-64
pubmed: 20051556
Nat Genet. 2011 Mar;43(3):242-5
pubmed: 21278745
Nature. 2005 Oct 27;437(7063):1299-320
pubmed: 16255080
Nat Struct Mol Biol. 2011 Feb;18(2):230-6
pubmed: 21258325
Nat Commun. 2012;3:1145
pubmed: 23093182
Hum Genome Var. 2019 Jun 18;6:28
pubmed: 31240104
Nat Genet. 2007 Oct;39(10):1217-24
pubmed: 17873874
Genome Res. 2012 Aug;22(8):1533-40
pubmed: 22499667
Nature. 2004 Sep 16;431(7006):350-5
pubmed: 15372042
Nat Commun. 2015 Mar 20;6:6601
pubmed: 25791433
Hum Mol Genet. 2011 Oct 15;20(20):4025-40
pubmed: 21807764
Nat Biotechnol. 2019 Jul;37(7):773-782
pubmed: 31061481
Nucleic Acids Res. 2018 Dec 14;46(22):11898-11909
pubmed: 30407537
Nucleic Acids Res. 2020 Jan 8;48(D1):D956-D963
pubmed: 31410488
RNA Biol. 2014;11(11):1375-85
pubmed: 25692236
Nucleic Acids Res. 2019 Jan 8;47(D1):D155-D162
pubmed: 30423142
Nat Genet. 2015 Mar;47(3):296-303
pubmed: 25621458
Nat Rev Genet. 2001 Nov;2(11):869-78
pubmed: 11715042
Nat Methods. 2015 Nov;12(11):1061-3
pubmed: 26366987
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Nucleic Acids Res. 2017 Sep 19;45(16):9290-9301
pubmed: 28934507
J Immunol. 2012 Feb 15;188(4):1573-7
pubmed: 22262659
Genome Res. 2017 Jul;27(7):1112-1125
pubmed: 28411194
Nat Genet. 2017 Jul;49(7):1120-1125
pubmed: 28553958
Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19678-83
pubmed: 19066217
Science. 2001 Oct 26;294(5543):862-4
pubmed: 11679672
Nat Genet. 2017 Oct;49(10):1458-1467
pubmed: 28892062
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
Nature. 2015 Oct 1;526(7571):75-81
pubmed: 26432246
Nat Biotechnol. 2017 Sep;35(9):872-878
pubmed: 28829439
Am J Hum Genet. 2018 Sep 6;103(3):338-348
pubmed: 30100085
Genome Biol. 2017 Jul 28;18(1):143
pubmed: 28754146
Bioinformatics. 2012 May 15;28(10):1353-8
pubmed: 22492648
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Nat Genet. 2007 May;39(5):673-7
pubmed: 17401365
Trends Genet. 2010 May;26(5):221-30
pubmed: 20395010
Cancer Genomics Proteomics. 2012 Mar-Apr;9(2):67-75
pubmed: 22399497
PLoS Genet. 2014 May 15;10(5):e1004383
pubmed: 24830394
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
Cell. 2004 Jan 23;116(2 Suppl):S89-92, 1 p following S96
pubmed: 15055592
Nat Rev Cancer. 2006 Apr;6(4):259-69
pubmed: 16557279
Sci Rep. 2016 Mar 01;6:22223
pubmed: 26927695
Science. 2020 Sep 11;369(6509):1318-1330
pubmed: 32913098
Nat Commun. 2018 Apr 24;9(1):1631
pubmed: 29691385
Cell. 1993 Dec 3;75(5):843-54
pubmed: 8252621
Science. 2007 Feb 9;315(5813):848-53
pubmed: 17289997
Nat Protoc. 2012 Feb 16;7(3):500-7
pubmed: 22343431
Science. 2007 Feb 23;315(5815):1137-40
pubmed: 17322061
Nat Genet. 2020 Jul;52(7):669-679
pubmed: 32514122
Nucleic Acids Res. 2016 Aug 19;44(14):e123
pubmed: 27229138
Nature. 2013 Sep 26;501(7468):506-11
pubmed: 24037378
Nature. 2005 Jun 9;435(7043):834-8
pubmed: 15944708
Carcinogenesis. 2018 May 28;39(6):798-807
pubmed: 29506142
Genome Med. 2013 Nov 29;5(11):105
pubmed: 24289319
Nat Rev Genet. 2009 Oct;10(10):704-14
pubmed: 19763153
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
pubmed: 12883005
Nat Commun. 2019 Sep 27;10(1):4393
pubmed: 31562340
Nat Neurosci. 2019 Sep;22(9):1402-1412
pubmed: 31455887
Genome Res. 2011 Jan;21(1):68-73
pubmed: 21147911
Hum Mol Genet. 2013 Aug 1;22(15):3023-37
pubmed: 23562819
Nat Genet. 2017 May;49(5):692-699
pubmed: 28369037
Genome Res. 2014 May;24(5):850-9
pubmed: 24482540
Noncoding RNA. 2020 Jun 02;6(2):
pubmed: 32498345
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
J Immunol. 2013 Apr 1;190(7):3679-86
pubmed: 23440414
Science. 2009 Sep 4;325(5945):1246-50
pubmed: 19644074
J Autoimmun. 2018 Nov;94:83-89
pubmed: 30143393
PLoS Genet. 2012;8(5):e1002704
pubmed: 22589741