chromMAGMA: regulatory element-centric interrogation of risk variants.

Chromatin Female Genome-Wide Association Study Genomics Humans Ovary Regulatory Sequences, Nucleic Acid / genetics

Journal

Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869

Informations de publication

Date de publication:
10 2022
Historique:
received: 11 03 2022
revised: 07 06 2022
accepted: 08 06 2022
entrez: 1 7 2022
pubmed: 2 7 2022
medline: 8 7 2022
Statut: epublish

Résumé

Candidate causal risk variants from genome-wide association studies reside almost exclusively in noncoding regions of the genome and innovative approaches are necessary to understand their biological function. Multi-marker analysis of genomic annotation (MAGMA) is a widely used program that nominates candidate risk genes by mapping single-nucleotide polymorphism summary statistics from genome-wide association studies to gene bodies. We augmented MAGMA to create chromatin-MAGMA (chromMAGMA), a method to nominate candidate risk genes based on the presence of risk variants within noncoding regulatory elements (REs). We applied chromMAGMA to a genetic susceptibility dataset for epithelial ovarian cancer (EOC), a rare gynecologic malignancy characterized by high mortality. This identified 155 unique candidate EOC risk genes across five EOC histotypes; 83% (105/127) of high-grade serous ovarian cancer risk genes had not previously been implicated in this EOC histotype. Risk genes nominated by chromMAGMA converged on mRNA splicing and transcriptional dysregulation pathways. chromMAGMA is a pipeline that nominates candidate risk genes through a gene regulation-focused approach and helps interpret the biological mechanism of noncoding risk variants for complex diseases.

Identifiants

DOI: 10.26508/lsa.202201446 PMID: 35777959 PMC: PMC9251535
pubmed: 35777959
pii: 5/10/e202201446
doi: 10.26508/lsa.202201446
pmc: PMC9251535
pii:
doi:

Substances chimiques

Chromatin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM118288
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA087969
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA067262
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA176726
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : Medical Research Council
ID : MR/T043202/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA049449
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States

Informations de copyright

© 2022 Nameki et al.

Références

Oncotarget. 2017 Nov 27;8(65):108316-108332
pubmed: 29312534
Nat Commun. 2021 Apr 26;12(1):2442
pubmed: 33903593
Bioinformatics. 2016 Jan 15;32(2):283-5
pubmed: 26395773
Cell. 2013 Nov 7;155(4):934-47
pubmed: 24119843
HGG Adv. 2021 Jul 8;2(3):
pubmed: 34317694
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nucleic Acids Res. 2015 Jul 1;43(W1):W589-98
pubmed: 25897122
Pharmacol Ther. 2015 Aug;152:111-24
pubmed: 25960131
Database (Oxford). 2017 Jan 1;2017:
pubmed: 28605766
Nat Genet. 2016 Aug;48(8):895-903
pubmed: 27376235
Cancer Discov. 2016 Sep;6(9):1052-67
pubmed: 27432226
Nat Genet. 2017 May;49(5):680-691
pubmed: 28346442
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Hum Mol Genet. 2015 Jul 1;24(13):3595-607
pubmed: 25804953
PLoS One. 2013 Sep 09;8(9):e74562
pubmed: 24040285
Nat Genet. 2013 Apr;45(4):371-84, 384e1-2
pubmed: 23535731
Nat Genet. 2016 Aug;48(8):904-911
pubmed: 27376239
Blood. 2011 Dec 1;118(23):e180-3
pubmed: 22001389
Immunity. 2021 May 11;54(5):947-961.e8
pubmed: 33930308
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Br J Cancer. 2017 Feb 14;116(4):524-535
pubmed: 28103614
Int J Clin Exp Pathol. 2015 Jul 01;8(7):8305-10
pubmed: 26339401
Cell Rep. 2016 Aug 23;16(8):2061-2067
pubmed: 27524613
Nat Genet. 2018 May;50(5):668-681
pubmed: 29700475
Nat Commun. 2016 Sep 07;7:12675
pubmed: 27601076
Nat Commun. 2018 Mar 5;9(1):943
pubmed: 29507293
Nat Genet. 2019 Jan;51(1):63-75
pubmed: 30478444
Nat Chem Biol. 2013 Oct;9(10):643-50
pubmed: 23974116
CA Cancer J Clin. 2018 Jul;68(4):284-296
pubmed: 29809280
Am J Hum Genet. 2020 Oct 1;107(4):622-635
pubmed: 32946763
Int J Gynecol Pathol. 2008 Apr;27(2):161-74
pubmed: 18317227
Nat Genet. 2015 Feb;47(2):164-71
pubmed: 25581431
Nat Genet. 2010 Oct;42(10):874-9
pubmed: 20852632
Nat Commun. 2020 Apr 24;11(1):2020
pubmed: 32332753
Cancer Res. 2018 Sep 15;78(18):5419-5430
pubmed: 30054336
Nat Commun. 2019 Feb 8;10(1):670
pubmed: 30737407
Cell. 2013 Apr 11;153(2):307-19
pubmed: 23582322
Pharmacol Ther. 2021 Apr;220:107722
pubmed: 33137377
Cell. 2017 Jun 15;169(7):1177-1186
pubmed: 28622505
Nat Genet. 2021 Dec;53(12):1698-1711
pubmed: 34857954
Nucleic Acids Res. 2019 Jan 8;47(D1):D1005-D1012
pubmed: 30445434
Nat Neurosci. 2020 Apr;23(4):583-593
pubmed: 32152537
Nat Genet. 2019 May;51(5):815-823
pubmed: 31043753
Nat Genet. 2009 Sep;41(9):996-1000
pubmed: 19648919
Cell. 2017 Feb 9;168(4):629-643
pubmed: 28187285
Science. 2018 Oct 26;362(6413):
pubmed: 30361341
Nat Genet. 2013 Apr;45(4):362-70, 370e1-2
pubmed: 23535730
Nat Genet. 2010 Oct;42(10):880-4
pubmed: 20852633
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
PLoS One. 2013;8(1):e54359
pubmed: 23382893
Genes Cancer. 2010 Jun;1(6):555-9
pubmed: 21779458
Nat Genet. 2017 Dec;49(12):1779-1784
pubmed: 29083409
Eur J Immunogenet. 2002 Jun;29(3):273-4
pubmed: 12047366
Animal Model Exp Med. 2018 Sep 25;1(3):169-179
pubmed: 30891562
Nat Commun. 2015 Sep 22;6:8234
pubmed: 26391404
Nat Genet. 2019 Mar;51(3):404-413
pubmed: 30617256
Nat Genet. 2019 Dec;51(12):1664-1669
pubmed: 31784727
Nature. 2015 Dec 17;528(7582):418-21
pubmed: 26560027
Tissue Antigens. 2011 Nov;78(5):333-44
pubmed: 21988720
Front Cell Dev Biol. 2020 Jan 14;7:377
pubmed: 31993419
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666
Cancers (Basel). 2019 Aug 03;11(8):
pubmed: 31382546
Hum Mol Genet. 2015 Oct 15;24(R1):R102-10
pubmed: 26152199
Genomics. 2015 Sep;106(3):145-150
pubmed: 26072434
Nat Genet. 2015 Aug;47(8):888-97
pubmed: 26075790
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Nature. 2021 May;593(7858):238-243
pubmed: 33828297
Nature. 2012 Sep 6;489(7414):109-13
pubmed: 22955621
Cell. 2018 Feb 8;172(4):650-665
pubmed: 29425488
Gynecol Oncol. 2017 Dec;147(3):705-713
pubmed: 29054568
Sci Adv. 2021 Nov 26;7(48):eabf6123
pubmed: 34818047

Auteurs

Robbin Nameki (R)

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
ORCID: 0000-0002-2538-5694

Anamay Shetty (A)

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
School of Clinical Medicine, University of Cambridge, Cambridge, UK.
ORCID: 0000-0003-0564-7236

Eileen Dareng (E)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

Jonathan Tyrer (J)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
ORCID: 0000-0003-3724-4757

Xianzhi Lin (X)

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Paul Pharoah (P)

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

Rosario I Corona (RI)

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Siddhartha Kar (S)

Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Kate Lawrenson (K)

Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA kate.lawrenson@cshs.org.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
ORCID: 0000-0002-6469-2515

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › chromMAGMA: regulatory element-centric...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › chromMAGMA: regulatory element-centric...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › chromMAGMA: regulatory element-centric...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › chromMAGMA: regulatory element-centric...
questionsmedicales.fr › Système endocrine › Glandes endocrines › Gonades › Ovaire › chromMAGMA: regulatory element-centric...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › chromMAGMA: regulatory element-centric...