Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. / Fachal, Laura; Aschard, Hugues; Beesley, Jonathan; Barnes, Daniel R.; Allen, Jamie; Kar, Siddhartha; Pooley, Karen A.; Dennis, Joe; Michailidou, Kyriaki; Turman, Constance; Soucy, Penny; Lemaçon, Audrey; Lush, Michael; Tyrer, Jonathan P.; Ghoussaini, Maya; Marjaneh, Mahdi Moradi; Jiang, Xia; Agata, Simona; Aittomäki, Kristiina; Alonso, M. Rosario; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arason, Adalgeir; Arndt, Volker; Aronson, Kristan J.; Arun, Banu K.; Auber, Bernd; Auer, Paul L.; Azzollini, Jacopo; Balmaña, Judith; Barkardottir, Rosa B.; Barrowdale, Daniel; Beeghly-Fadiel, Alicia; Benitez, Javier; Bermisheva, Marina; Białkowska, Katarzyna; Blanco, Amie M.; Blomqvist, Carl; Blot, William; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borg, Ake; Bosse, Kristin; Brauch, Hiltrud; Flyger, Henrik; Nielsen, Finn C.; Wang, Qin; ABCTB Investigators; GEMO Study Collaborators; EMBRACE Collaborators; kConFab Investigators; HEBON Investigators.

I: Nature Genetics, Bind 52, Nr. 1, 2020, s. 56-73.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Fachal, L, Aschard, H, Beesley, J, Barnes, DR, Allen, J, Kar, S, Pooley, KA, Dennis, J, Michailidou, K, Turman, C, Soucy, P, Lemaçon, A, Lush, M, Tyrer, JP, Ghoussaini, M, Marjaneh, MM, Jiang, X, Agata, S, Aittomäki, K, Alonso, MR, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Arason, A, Arndt, V, Aronson, KJ, Arun, BK, Auber, B, Auer, PL, Azzollini, J, Balmaña, J, Barkardottir, RB, Barrowdale, D, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Białkowska, K, Blanco, AM, Blomqvist, C, Blot, W, Bogdanova, NV, Bojesen, SE, Bolla, MK, Bonanni, B, Borg, A, Bosse, K, Brauch, H, Flyger, H, Nielsen, FC, Wang, Q, ABCTB Investigators, GEMO Study Collaborators, EMBRACE Collaborators, kConFab Investigators & HEBON Investigators 2020, 'Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes', Nature Genetics, bind 52, nr. 1, s. 56-73. https://doi.org/10.1038/s41588-019-0537-1

APA

Fachal, L., Aschard, H., Beesley, J., Barnes, D. R., Allen, J., Kar, S., Pooley, K. A., Dennis, J., Michailidou, K., Turman, C., Soucy, P., Lemaçon, A., Lush, M., Tyrer, J. P., Ghoussaini, M., Marjaneh, M. M., Jiang, X., Agata, S., Aittomäki, K., ... HEBON Investigators (2020). Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics, 52(1), 56-73. https://doi.org/10.1038/s41588-019-0537-1

Vancouver

Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S o.a. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics. 2020;52(1):56-73. https://doi.org/10.1038/s41588-019-0537-1

Author

Fachal, Laura ; Aschard, Hugues ; Beesley, Jonathan ; Barnes, Daniel R. ; Allen, Jamie ; Kar, Siddhartha ; Pooley, Karen A. ; Dennis, Joe ; Michailidou, Kyriaki ; Turman, Constance ; Soucy, Penny ; Lemaçon, Audrey ; Lush, Michael ; Tyrer, Jonathan P. ; Ghoussaini, Maya ; Marjaneh, Mahdi Moradi ; Jiang, Xia ; Agata, Simona ; Aittomäki, Kristiina ; Alonso, M. Rosario ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Antonenkova, Natalia N. ; Arason, Adalgeir ; Arndt, Volker ; Aronson, Kristan J. ; Arun, Banu K. ; Auber, Bernd ; Auer, Paul L. ; Azzollini, Jacopo ; Balmaña, Judith ; Barkardottir, Rosa B. ; Barrowdale, Daniel ; Beeghly-Fadiel, Alicia ; Benitez, Javier ; Bermisheva, Marina ; Białkowska, Katarzyna ; Blanco, Amie M. ; Blomqvist, Carl ; Blot, William ; Bogdanova, Natalia V. ; Bojesen, Stig E. ; Bolla, Manjeet K. ; Bonanni, Bernardo ; Borg, Ake ; Bosse, Kristin ; Brauch, Hiltrud ; Flyger, Henrik ; Nielsen, Finn C. ; Wang, Qin ; ABCTB Investigators ; GEMO Study Collaborators ; EMBRACE Collaborators ; kConFab Investigators ; HEBON Investigators. / Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. I: Nature Genetics. 2020 ; Bind 52, Nr. 1. s. 56-73.

Bibtex

@article{fa65af678754401f9858093e2e2f2981,
title = "Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes",
abstract = "Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.",
author = "Laura Fachal and Hugues Aschard and Jonathan Beesley and Barnes, {Daniel R.} and Jamie Allen and Siddhartha Kar and Pooley, {Karen A.} and Joe Dennis and Kyriaki Michailidou and Constance Turman and Penny Soucy and Audrey Lema{\c c}on and Michael Lush and Tyrer, {Jonathan P.} and Maya Ghoussaini and Marjaneh, {Mahdi Moradi} and Xia Jiang and Simona Agata and Kristiina Aittom{\"a}ki and Alonso, {M. Rosario} and Andrulis, {Irene L.} and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Adalgeir Arason and Volker Arndt and Aronson, {Kristan J.} and Arun, {Banu K.} and Bernd Auber and Auer, {Paul L.} and Jacopo Azzollini and Judith Balma{\~n}a and Barkardottir, {Rosa B.} and Daniel Barrowdale and Alicia Beeghly-Fadiel and Javier Benitez and Marina Bermisheva and Katarzyna Bia{\l}kowska and Blanco, {Amie M.} and Carl Blomqvist and William Blot and Bogdanova, {Natalia V.} and Bojesen, {Stig E.} and Bolla, {Manjeet K.} and Bernardo Bonanni and Ake Borg and Kristin Bosse and Hiltrud Brauch and Henrik Flyger and Nielsen, {Finn C.} and Qin Wang and {ABCTB Investigators} and {GEMO Study Collaborators} and {EMBRACE Collaborators} and {kConFab Investigators} and {HEBON Investigators}",
year = "2020",
doi = "10.1038/s41588-019-0537-1",
language = "English",
volume = "52",
pages = "56--73",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

AU - Fachal, Laura

AU - Aschard, Hugues

AU - Beesley, Jonathan

AU - Barnes, Daniel R.

AU - Allen, Jamie

AU - Kar, Siddhartha

AU - Pooley, Karen A.

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - Turman, Constance

AU - Soucy, Penny

AU - Lemaçon, Audrey

AU - Lush, Michael

AU - Tyrer, Jonathan P.

AU - Ghoussaini, Maya

AU - Marjaneh, Mahdi Moradi

AU - Jiang, Xia

AU - Agata, Simona

AU - Aittomäki, Kristiina

AU - Alonso, M. Rosario

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arason, Adalgeir

AU - Arndt, Volker

AU - Aronson, Kristan J.

AU - Arun, Banu K.

AU - Auber, Bernd

AU - Auer, Paul L.

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barkardottir, Rosa B.

AU - Barrowdale, Daniel

AU - Beeghly-Fadiel, Alicia

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Białkowska, Katarzyna

AU - Blanco, Amie M.

AU - Blomqvist, Carl

AU - Blot, William

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Bonanni, Bernardo

AU - Borg, Ake

AU - Bosse, Kristin

AU - Brauch, Hiltrud

AU - Flyger, Henrik

AU - Nielsen, Finn C.

AU - Wang, Qin

AU - ABCTB Investigators

AU - GEMO Study Collaborators

AU - EMBRACE Collaborators

AU - kConFab Investigators

AU - HEBON Investigators

PY - 2020

Y1 - 2020

N2 - Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.

AB - Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.

U2 - 10.1038/s41588-019-0537-1

DO - 10.1038/s41588-019-0537-1

M3 - Journal article

C2 - 31911677

AN - SCOPUS:85077675544

VL - 52

SP - 56

EP - 73

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 1

ER -

ID: 235777262