Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

Chen, Hongjie; Fan, Shaoqi; Stone, Jennifer; Thompson, Deborah J; Douglas, Julie; Li, Shuai; Scott, Christopher; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Li, Christopher; Peters, Ulrike; Hopper, John L; Southey, Melissa C; Nguyen-Dumont, Tu; Nguyen, Tuong L; Fasching, Peter A; Behrens, Annika; Cadby, Gemma; Murphy, Rachel A; Aronson, Kristan; Howell, Anthony; Astley, Susan; Couch, Fergus; Olson, Janet; Milne, Roger L; Giles, Graham G; Haiman, Christopher A; Maskarinec, Gertraud; Winham, Stacey; John, Esther M; Kurian, Allison; Eliassen, Heather; Andrulis, Irene; Evans, D Gareth; Newman, William G; Hall, Per; Czene, Kamila; Swerdlow, Anthony; Jones, Michael; Pollan-Santamaria, Marina; Fernandez-Navarro, Pablo L; McConnell, Daniel S; Kristensen, Vessela N; Rothstein, Joseph H; Wang, Pei; Habel, Laurel A; Sieh, Weiva; Dunning, Alison M; Pharoah, Paul D P; Easton, Douglas F; Gierach, Gretchen L; Tamimi, Rulla M; Vachon, Celine M; Lindström, Sara

Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

Background: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance i...

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Autores:	Chen, Hongjie, Fan, Shaoqi, Stone, Jennifer, Thompson, Deborah J, Douglas, Julie, Li, Shuai, Scott, Christopher, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Michailidou, Kyriaki, Li, Christopher, Peters, Ulrike, Hopper, John L, Southey, Melissa C, Nguyen-Dumont, Tu, Nguyen, Tuong L, Fasching, Peter A, Behrens, Annika, Cadby, Gemma, Murphy, Rachel A, Aronson, Kristan, Howell, Anthony, Astley, Susan, Couch, Fergus, Olson, Janet, Milne, Roger L, Giles, Graham G, Haiman, Christopher A, Maskarinec, Gertraud, Winham, Stacey, John, Esther M, Kurian, Allison, Eliassen, Heather, Andrulis, Irene, Evans, D Gareth, Newman, William G, Hall, Per, Czene, Kamila, Swerdlow, Anthony, Jones, Michael, Pollan-Santamaria, Marina, Fernandez-Navarro, Pablo L, McConnell, Daniel S, Kristensen, Vessela N, Rothstein, Joseph H, Wang, Pei, Habel, Laurel A, Sieh, Weiva, Dunning, Alison M, Pharoah, Paul D P, Easton, Douglas F, Gierach, Gretchen L, Tamimi, Rulla M, Vachon, Celine M, Lindström, Sara
Tipo de recurso:	artículo
Fecha de publicación:	2022
País:	España
Institución:	Instituto de Salud Carlos III (ISCIII)
Repositorio:	Repisalud
Idioma:	inglés
OAI Identifier:	oai:repisalud.isciii.es:20.500.12105/14868
Acceso en línea:	http://hdl.handle.net/20.500.12105/14868
Access Level:	acceso abierto
Palabra clave:	Breast Density Breast Neoplasms Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Phenotype Polymorphism, Single Nucleotide Transcriptome

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oai_identifier_str	oai:repisalud.isciii.es:20.500.12105/14868
network_acronym_str	ES
network_name_str	España
repository_id_str
dc.title.none.fl_str_mv	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
title	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
spellingShingle	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci Chen, Hongjie Breast Density Breast Neoplasms Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Phenotype Polymorphism, Single Nucleotide Transcriptome
title_short	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
title_full	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
title_fullStr	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
title_full_unstemmed	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
title_sort	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
dc.creator.none.fl_str_mv	Chen, Hongjie Fan, Shaoqi Stone, Jennifer Thompson, Deborah J Douglas, Julie Li, Shuai Scott, Christopher Bolla, Manjeet K Wang, Qin Dennis, Joe Michailidou, Kyriaki Li, Christopher Peters, Ulrike Hopper, John L Southey, Melissa C Nguyen-Dumont, Tu Nguyen, Tuong L Fasching, Peter A Behrens, Annika Cadby, Gemma Murphy, Rachel A Aronson, Kristan Howell, Anthony Astley, Susan Couch, Fergus Olson, Janet Milne, Roger L Giles, Graham G Haiman, Christopher A Maskarinec, Gertraud Winham, Stacey John, Esther M Kurian, Allison Eliassen, Heather Andrulis, Irene Evans, D Gareth Newman, William G Hall, Per Czene, Kamila Swerdlow, Anthony Jones, Michael Pollan-Santamaria, Marina Fernandez-Navarro, Pablo L McConnell, Daniel S Kristensen, Vessela N Rothstein, Joseph H Wang, Pei Habel, Laurel A Sieh, Weiva Dunning, Alison M Pharoah, Paul D P Easton, Douglas F Gierach, Gretchen L Tamimi, Rulla M Vachon, Celine M Lindström, Sara
author	Chen, Hongjie
author_facet	Chen, Hongjie Fan, Shaoqi Stone, Jennifer Thompson, Deborah J Douglas, Julie Li, Shuai Scott, Christopher Bolla, Manjeet K Wang, Qin Dennis, Joe Michailidou, Kyriaki Li, Christopher Peters, Ulrike Hopper, John L Southey, Melissa C Nguyen-Dumont, Tu Nguyen, Tuong L Fasching, Peter A Behrens, Annika Cadby, Gemma Murphy, Rachel A Aronson, Kristan Howell, Anthony Astley, Susan Couch, Fergus Olson, Janet Milne, Roger L Giles, Graham G Haiman, Christopher A Maskarinec, Gertraud Winham, Stacey John, Esther M Kurian, Allison Eliassen, Heather Andrulis, Irene Evans, D Gareth Newman, William G Hall, Per Czene, Kamila Swerdlow, Anthony Jones, Michael Pollan-Santamaria, Marina Fernandez-Navarro, Pablo L McConnell, Daniel S Kristensen, Vessela N Rothstein, Joseph H Wang, Pei Habel, Laurel A Sieh, Weiva Dunning, Alison M Pharoah, Paul D P Easton, Douglas F Gierach, Gretchen L Tamimi, Rulla M Vachon, Celine M Lindström, Sara
author_role	author
author2	Fan, Shaoqi Stone, Jennifer Thompson, Deborah J Douglas, Julie Li, Shuai Scott, Christopher Bolla, Manjeet K Wang, Qin Dennis, Joe Michailidou, Kyriaki Li, Christopher Peters, Ulrike Hopper, John L Southey, Melissa C Nguyen-Dumont, Tu Nguyen, Tuong L Fasching, Peter A Behrens, Annika Cadby, Gemma Murphy, Rachel A Aronson, Kristan Howell, Anthony Astley, Susan Couch, Fergus Olson, Janet Milne, Roger L Giles, Graham G Haiman, Christopher A Maskarinec, Gertraud Winham, Stacey John, Esther M Kurian, Allison Eliassen, Heather Andrulis, Irene Evans, D Gareth Newman, William G Hall, Per Czene, Kamila Swerdlow, Anthony Jones, Michael Pollan-Santamaria, Marina Fernandez-Navarro, Pablo L McConnell, Daniel S Kristensen, Vessela N Rothstein, Joseph H Wang, Pei Habel, Laurel A Sieh, Weiva Dunning, Alison M Pharoah, Paul D P Easton, Douglas F Gierach, Gretchen L Tamimi, Rulla M Vachon, Celine M Lindström, Sara
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Unión Europea. Comisión Europea. H2020 Canadian Institutes of Health Research Quebec Breast Cancer Foundation Government of Quebec (Canadá) National Institutes of Health (Estados Unidos) Unión Europea. Comisión Europea. 7 Programa Marco Cancer Research UK (Reino Unido) Susan G. Komen Breast Cancer Foundation Ovarian Cancer Research Foundation (Astrualia) Australian Breast Cancer Family Study NIH - National Cancer Institute (NCI) (Estados Unidos) National Health and Medical Research Council (Australia) New South Wales Cancer Council (Reino Unido) Victorian Cancer Agency National Breast Cancer Foundation (Australia) Cancer Australia Universitätsklinikum Erlangen (Alemania) Consorcio Gallego de Cáncer de Mama (BREOGAN) Instituto de Salud Carlos III Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) Galicia Sur Biomedical Foundation Xunta de Galicia (España) Ministerio de Sanidad, Servicios Sociales e Igualdad (España) Ministerio de Economía y Competitividad (España) Canadian Cancer Society NIHR - Manchester Biomedical Research Centre (Reino Unido) Cancer Council New South Wales (Australia) Cancer Council Victoria (Australia) Cancer Council Tasmania (Australia) Cancer Council South (Australia) Cancer Council Western Australia (Australia) United States Army Medical Research and Development Command Cancer Council Queensland (Australia) NIH - NCI-Specialized Programs of Research Excellence (SPORE) in Breast Cancer (Estados Unidos) Victorian Health Promotion Foundation The Research Council of Norway (Noruega) Southern and Eastern Norway Regional Health Authority Norwegian Cancer Society Agency for Science, Technology and Research (Singapur) Institute of Cancer Research (Reino Unido) NIHR - Manchester Biomedical Research Centre (Reino Unido)
dc.subject.none.fl_str_mv	Breast Density Breast Neoplasms Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Phenotype Polymorphism, Single Nucleotide Transcriptome
topic	Breast Density Breast Neoplasms Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Phenotype Polymorphism, Single Nucleotide Transcriptome
description	Background: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. Methods: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. Results: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. Conclusions: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.
publishDate	2022
dc.date.none.fl_str_mv	2022 2022-08-05 2022 2022-04-12 2022 2022-04-12
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.12105/14868
url	http://hdl.handle.net/20.500.12105/14868
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 634935 European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 633784 European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 223175
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
dc.publisher.none.fl_str_mv	BioMed Central (BMC)
publisher.none.fl_str_mv	BioMed Central (BMC)
dc.source.none.fl_str_mv	reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII)
instname_str	Instituto de Salud Carlos III (ISCIII)
reponame_str	Repisalud
collection	Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling	Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel lociChen, HongjieFan, ShaoqiStone, JenniferThompson, Deborah JDouglas, JulieLi, ShuaiScott, ChristopherBolla, Manjeet KWang, QinDennis, JoeMichailidou, KyriakiLi, ChristopherPeters, UlrikeHopper, John LSouthey, Melissa CNguyen-Dumont, TuNguyen, Tuong LFasching, Peter ABehrens, AnnikaCadby, GemmaMurphy, Rachel AAronson, KristanHowell, AnthonyAstley, SusanCouch, FergusOlson, JanetMilne, Roger LGiles, Graham GHaiman, Christopher AMaskarinec, GertraudWinham, StaceyJohn, Esther MKurian, AllisonEliassen, HeatherAndrulis, IreneEvans, D GarethNewman, William GHall, PerCzene, KamilaSwerdlow, AnthonyJones, MichaelPollan-Santamaria, MarinaFernandez-Navarro, Pablo LMcConnell, Daniel SKristensen, Vessela NRothstein, Joseph HWang, PeiHabel, Laurel ASieh, WeivaDunning, Alison MPharoah, Paul D PEaston, Douglas FGierach, Gretchen LTamimi, Rulla MVachon, Celine MLindström, SaraBreast DensityBreast NeoplasmsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideTranscriptomeBackground: Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. Methods: We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. Results: We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. Conclusions: Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.BioMed Central (BMC)Unión Europea. Comisión Europea. H2020Canadian Institutes of Health ResearchQuebec Breast Cancer FoundationGovernment of Quebec (Canadá)National Institutes of Health (Estados Unidos)Unión Europea. Comisión Europea. 7 Programa MarcoCancer Research UK (Reino Unido)Susan G. Komen Breast Cancer FoundationOvarian Cancer Research Foundation (Astrualia)Australian Breast Cancer Family StudyNIH - National Cancer Institute (NCI) (Estados Unidos)National Health and Medical Research Council (Australia)New South Wales Cancer Council (Reino Unido)Victorian Cancer AgencyNational Breast Cancer Foundation (Australia)Cancer AustraliaUniversitätsklinikum Erlangen (Alemania)Consorcio Gallego de Cáncer de Mama (BREOGAN)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Galicia Sur Biomedical FoundationXunta de Galicia (España)Ministerio de Sanidad, Servicios Sociales e Igualdad (España)Ministerio de Economía y Competitividad (España)Canadian Cancer SocietyNIHR - Manchester Biomedical Research Centre (Reino Unido)Cancer Council New South Wales (Australia)Cancer Council Victoria (Australia)Cancer Council Tasmania (Australia)Cancer Council South (Australia)Cancer Council Western Australia (Australia)United States Army Medical Research and Development CommandCancer Council Queensland (Australia)NIH - NCI-Specialized Programs of Research Excellence (SPORE) in Breast Cancer (Estados Unidos)Victorian Health Promotion FoundationThe Research Council of Norway (Noruega)Southern and Eastern Norway Regional Health AuthorityNorwegian Cancer SocietyAgency for Science, Technology and Research (Singapur)Institute of Cancer Research (Reino Unido)NIHR - Manchester Biomedical Research Centre (Reino Unido)20222022-08-0520222022-04-1220222022-04-12journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheethttp://hdl.handle.net/20.500.12105/14868reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 634935European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 633784European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 223175open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/148682026-06-12T12:43:37Z
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Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci

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