Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 12 2022
08 12 2022
Historique:
received:
21
12
2021
accepted:
29
11
2022
entrez:
9
12
2022
pubmed:
10
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits and observed 21 independent signals (12 common and 9 rare) reaching genome-wide significance. The majority of these associations (N = 18) replicated in independent datasets. In genome-editing experiments, we provide evidence that a deletion associated with lower monocyte counts leads to disruption of an S1PR3 monocyte enhancer and decreased S1PR3 expression.
Identifiants
pubmed: 36481753
doi: 10.1038/s41467-022-35354-7
pii: 10.1038/s41467-022-35354-7
pmc: PMC9732337
doi:
Substances chimiques
sphingosine-1-phosphate receptor-3, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7592Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL154385
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007018
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011720
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Nat Genet. 2015 Mar;47(3):284-90
pubmed: 25642633
Control Clin Trials. 1998 Feb;19(1):61-109
pubmed: 9492970
Am J Hum Genet. 2019 Aug 1;105(2):373-383
pubmed: 31353025
Am J Hum Genet. 2021 Apr 1;108(4):583-596
pubmed: 33798444
Nat Commun. 2017 Jan 24;8:14061
pubmed: 28117401
Brief Bioinform. 2021 Nov 5;22(6):
pubmed: 34015820
PLoS Genet. 2018 Mar 28;14(3):e1007293
pubmed: 29590102
Annu Rev Med. 2010;61:437-55
pubmed: 20059347
Nat Commun. 2021 Feb 1;12(1):730
pubmed: 33526789
Nat Genet. 2016 Apr;48(4):359-66
pubmed: 26901066
Bioinformatics. 2021 Mar 24;:
pubmed: 33760063
Genet Epidemiol. 2015 May;39(4):276-93
pubmed: 25810074
Am J Epidemiol. 1989 Apr;129(4):687-702
pubmed: 2646917
Ann Epidemiol. 1991 Feb;1(3):263-76
pubmed: 1669507
Nature. 2015 Oct 1;526(7571):75-81
pubmed: 26432246
Cell. 2014 Dec 18;159(7):1665-80
pubmed: 25497547
Nat Genet. 2008 Sep;40(9):1068-75
pubmed: 19165921
Orphanet J Rare Dis. 2010 May 28;5:13
pubmed: 20507641
Biochem Biophys Res Commun. 2002 May 10;293(3):1124-31
pubmed: 12051776
Nat Commun. 2017 May 05;8:15178
pubmed: 28474669
Nucleic Acids Res. 2019 Jul 2;47(W1):W158-W165
pubmed: 31165883
Am J Hum Genet. 2016 Jan 7;98(1):127-48
pubmed: 26748516
Genet Med. 2013 Oct;15(10):761-71
pubmed: 23743551
Nat Genet. 2015 May;47(5):435-44
pubmed: 25807286
Bioinformatics. 2012 May 15;28(10):1353-8
pubmed: 22492648
Genet Epidemiol. 2019 Jun;43(4):365-372
pubmed: 30623491
Immunology. 2020 Jul;160(3):233-247
pubmed: 32031242
Int J Mol Sci. 2020 Dec 19;21(24):
pubmed: 33352721
Am J Hum Genet. 2021 Oct 7;108(10):1836-1851
pubmed: 34582791
Am J Hum Genet. 2021 Jun 3;108(6):1165
pubmed: 34087167
Blood. 2010 Feb 11;115(6):1264-6
pubmed: 20007542
Am Heart J. 2008 May;155(5):823-8
pubmed: 18440328
Bioinformatics. 2018 Mar 1;34(5):867-868
pubmed: 29096012
Nat Commun. 2019 Nov 27;10(1):5402
pubmed: 31776332
Cell. 2016 Nov 17;167(5):1415-1429.e19
pubmed: 27863252
Nat Commun. 2018 Oct 2;9(1):4038
pubmed: 30279509
Cell. 2016 Nov 17;167(5):1369-1384.e19
pubmed: 27863249
Hum Mol Genet. 2022 Feb 3;31(3):347-361
pubmed: 34553764
Am J Epidemiol. 2002 Nov 1;156(9):871-81
pubmed: 12397006
Hum Mol Genet. 2013 Jun 15;22(12):2529-38
pubmed: 23446634
Bioinformatics. 2017 Dec 01;33(23):3793-3795
pubmed: 28582503
Ethn Dis. 2005 Autumn;15(4 Suppl 6):S6-30-37
pubmed: 16317983
Mol Cell. 2017 Sep 21;67(6):1037-1048.e6
pubmed: 28890333
Bioinformatics. 2019 Dec 15;35(24):5346-5348
pubmed: 31329242
Cell. 2020 Sep 3;182(5):1198-1213.e14
pubmed: 32888493
Ethn Dis. 2005 Autumn;15(4 Suppl 6):S6-4-17
pubmed: 16320381
Cell Rep. 2016 Nov 15;17(8):2042-2059
pubmed: 27851967
Am J Hum Genet. 2019 Oct 3;105(4):763-772
pubmed: 31564439
Gigascience. 2020 Dec 21;9(12):
pubmed: 33347570
Cell Mol Bioeng. 2018 Aug;11(4):241-253
pubmed: 29983824
Am J Epidemiol. 2007 Jun 1;165(11):1328-35
pubmed: 17372189
Nat Genet. 2021 Jun;53(6):779-786
pubmed: 33972781
Cell. 2020 Sep 3;182(5):1214-1231.e11
pubmed: 32888494
Nature. 2020 Jul;583(7814):96-102
pubmed: 32581362
Control Clin Trials. 1987 Dec;8(4 Suppl):68S-73S
pubmed: 3440391
Blood. 2020 Dec 3;136(23):2679-2690
pubmed: 32663239
Comput Struct Biotechnol J. 2020 Dec 29;19:355-362
pubmed: 33489005
JAMA. 2006 Mar 22;295(12):1420-7
pubmed: 16551714
Nat Methods. 2015 Oct;12(10):966-8
pubmed: 26258291
Nat Med. 2019 May;25(5):776-783
pubmed: 30911135
Bioinformatics. 2018 Oct 15;34(20):3572-3574
pubmed: 29669011
COPD. 2010 Feb;7(1):32-43
pubmed: 20214461
Nat Genet. 2017 May;49(5):692-699
pubmed: 28369037
Blood Cancer Discov. 2021 Jan 1;2(1):32-53
pubmed: 33458693
Science. 2004 Oct 22;306(5696):636-40
pubmed: 15499007
Blood. 2021 Feb 18;137(7):959-968
pubmed: 33094331
Ann Epidemiol. 2010 Aug;20(8):629-41
pubmed: 20609343
PLoS Genet. 2022 Jan 31;18(1):e1009984
pubmed: 35100265
Am J Hum Genet. 2019 Nov 7;105(5):947-958
pubmed: 31668704
Nat Commun. 2020 Jun 10;11(1):2927
pubmed: 32522982
Nature. 2021 Feb;590(7845):290-299
pubmed: 33568819
Genet Epidemiol. 2019 Apr;43(3):263-275
pubmed: 30653739
Stem Cells. 2017 Apr;35(4):1040-1052
pubmed: 28026131
Nat Rev Genet. 2013 Feb;14(2):125-38
pubmed: 23329113