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Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

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Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. / Orr, Nick; Dudbridge, Frank; Dryden, Nicola; Maguire, Sarah; Novo, Daniela; Perrakis, Eleni; Johnson, Nichola; Ghoussaini, Maya; Hopper, John L; Southey, Melissa C; Apicella, Carmel; Stone, Jennifer; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Hogervorst, Frans B; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Gibson, Lorna; Aitken, Zoe; Warren, Helen; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Chistof; Guénel, Pascal; Truong, Thérèse; Cordina-Duverger, Emilie; Sanchez, Marie; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, Maria Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Hamann, Ute; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Ko, Yon-Dschun; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Bogdanova, Natalia; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Beesley, Jonathan; Lambrechts, Diether; Moisse, Matthieu; Floris, Guiseppe; Beuselinck, Benoit; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Peissel, Bernard; Pensotti, Valeria; Couch, Fergus J; Olson, Janet E; Slettedahl, Seth; Vachon, Celine; Giles, Graham G; Milne, Roger L; McLean, Catriona; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Alnæs, Grethe Grenaker; Nord, Silje; Borresen-Dale, Anne-Lise; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Van Asperen, Christi J; Garcia-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Klevebring, Daniel; Hooning, Maartje J; Hollestelle, Antoinette; van Deurzen, Carolien H M; Kriege, Mieke; Hall, Per; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Perkins, Barbara J; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Schoemaker, Minouk J; Meindl, Alfons; Schmutzler, Rita K; Olswold, Curtis; Slager, Susan; Toland, Amanda E; Yannoukakos, Drakoulis; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Matsuo, Keitaro; Ito, Hidema; Iwata, Hiroji; Ishiguro, Junko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Teo, Soo Hwang; Yip, Cheng Har; Kang, Peter; Ikram, Mohammad Kamran; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Noh, Dong-Young; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Lee, Soo Chin; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Wu, Pei-Ei; Hou, Ming-Feng; Yu, Jyh-Cherng; Shen, Chen-Yang; Blot, William; Cai, Qiuyin; Signorello, Lisa B; Luccarini, Craig; Bayes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Hunter, David J; Lindstrom, Sara; Dennis, Joe; Michailidou, Kyriaki; Bolla, Manjeet K; Easton, Douglas F; dos Santos Silva, Isabel; Fletcher, Olivia; Peto, Julian; GENICA Network.

In: HUM MOL GENET, Vol. 24, No. 10, 15.05.2015, p. 2966-84.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Orr, N, Dudbridge, F, Dryden, N, Maguire, S, Novo, D, Perrakis, E, Johnson, N, Ghoussaini, M, Hopper, JL, Southey, MC, Apicella, C, Stone, J, Schmidt, MK, Broeks, A, Van't Veer, LJ, Hogervorst, FB, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Gibson, L, Aitken, Z, Warren, H, Sawyer, E, Tomlinson, I, Kerin, MJ, Miller, N, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Guénel, P, Truong, T, Cordina-Duverger, E, Sanchez, M, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Benitez, J, Zamora, MP, Arias Perez, JI, Menéndez, P, Anton-Culver, H, Neuhausen, SL, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Hamann, U, Brauch, H, Justenhoven, C, Brüning, T, Ko, Y-D, Nevanlinna, H, Aittomäki, K, Blomqvist, C, Khan, S, Bogdanova, N, Dörk, T, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Chenevix-Trench, G, Beesley, J, Lambrechts, D, Moisse, M, Floris, G, Beuselinck, B, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Radice, P, Peterlongo, P, Peissel, B, Pensotti, V, Couch, FJ, Olson, JE, Slettedahl, S, Vachon, C, Giles, GG, Milne, RL, McLean, C, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Simard, J, Goldberg, MS, Labrèche, F, Dumont, M, Kristensen, V, Alnæs, GG, Nord, S, Borresen-Dale, A-L, Zheng, W, Deming-Halverson, S, Shrubsole, M, Long, J, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, RAEM, Seynaeve, CM, Van Asperen, CJ, Garcia-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Czene, K, Darabi, H, Eriksson, M, Klevebring, D, Hooning, MJ, Hollestelle, A, van Deurzen, CHM, Kriege, M, Hall, P, Li, J, Liu, J, Humphreys, K, Cox, A, Cross, SS, Reed, MWR, Pharoah, PDP, Dunning, AM, Shah, M, Perkins, BJ, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Ashworth, A, Swerdlow, A, Jones, M, Schoemaker, MJ, Meindl, A, Schmutzler, RK, Olswold, C, Slager, S, Toland, AE, Yannoukakos, D, Muir, K, Lophatananon, A, Stewart-Brown, S, Siriwanarangsan, P, Matsuo, K, Ito, H, Iwata, H, Ishiguro, J, Wu, AH, Tseng, C-C, Van Den Berg, D, Stram, DO, Teo, SH, Yip, CH, Kang, P, Ikram, MK, Shu, X-O, Lu, W, Gao, Y-T, Cai, H, Kang, D, Choi, J-Y, Park, SK, Noh, D-Y, Hartman, M, Miao, H, Lim, WY, Lee, SC, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Wu, P-E, Hou, M-F, Yu, J-C, Shen, C-Y, Blot, W, Cai, Q, Signorello, LB, Luccarini, C, Bayes, C, Ahmed, S, Maranian, M, Healey, CS, González-Neira, A, Pita, G, Alonso, MR, Álvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Hunter, DJ, Lindstrom, S, Dennis, J, Michailidou, K, Bolla, MK, Easton, DF, dos Santos Silva, I, Fletcher, O, Peto, J & GENICA Network 2015, 'Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2', HUM MOL GENET, vol. 24, no. 10, pp. 2966-84. https://doi.org/10.1093/hmg/ddv035

APA

Orr, N., Dudbridge, F., Dryden, N., Maguire, S., Novo, D., Perrakis, E., Johnson, N., Ghoussaini, M., Hopper, J. L., Southey, M. C., Apicella, C., Stone, J., Schmidt, M. K., Broeks, A., Van't Veer, L. J., Hogervorst, F. B., Fasching, P. A., Haeberle, L., Ekici, A. B., ... GENICA Network (2015). Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. HUM MOL GENET, 24(10), 2966-84. https://doi.org/10.1093/hmg/ddv035

Vancouver

Orr N, Dudbridge F, Dryden N, Maguire S, Novo D, Perrakis E et al. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2. HUM MOL GENET. 2015 May 15;24(10):2966-84. https://doi.org/10.1093/hmg/ddv035

Bibtex

@article{df754cb608ac4662aaf0dedfc01f4787,
title = "Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2",
abstract = "We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.",
author = "Nick Orr and Frank Dudbridge and Nicola Dryden and Sarah Maguire and Daniela Novo and Eleni Perrakis and Nichola Johnson and Maya Ghoussaini and Hopper, {John L} and Southey, {Melissa C} and Carmel Apicella and Jennifer Stone and Schmidt, {Marjanka K} and Annegien Broeks and {Van't Veer}, {Laura J} and Hogervorst, {Frans B} and Fasching, {Peter A} and Lothar Haeberle and Ekici, {Arif B} and Beckmann, {Matthias W} and Lorna Gibson and Zoe Aitken and Helen Warren and Elinor Sawyer and Ian Tomlinson and Kerin, {Michael J} and Nicola Miller and Barbara Burwinkel and Frederik Marme and Andreas Schneeweiss and Chistof Sohn and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Emilie Cordina-Duverger and Marie Sanchez and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G} and Nielsen, {Sune F} and Henrik Flyger and Javier Benitez and Zamora, {Maria Pilar} and {Arias Perez}, {Jose Ignacio} and Primitiva Men{\'e}ndez and Hoda Anton-Culver and Neuhausen, {Susan L} and Hermann Brenner and Dieffenbach, {Aida Karina} and Volker Arndt and Christa Stegmaier and Ute Hamann and Hiltrud Brauch and Christina Justenhoven and Thomas Br{\"u}ning and Yon-Dschun Ko and Heli Nevanlinna and Kristiina Aittom{\"a}ki and Carl Blomqvist and Sofia Khan and Natalia Bogdanova and Thilo D{\"o}rk and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M} and Georgia Chenevix-Trench and Jonathan Beesley and Diether Lambrechts and Matthieu Moisse and Guiseppe Floris and Benoit Beuselinck and Jenny Chang-Claude and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Paolo Radice and Paolo Peterlongo and Bernard Peissel and Valeria Pensotti and Couch, {Fergus J} and Olson, {Janet E} and Seth Slettedahl and Celine Vachon and Giles, {Graham G} and Milne, {Roger L} and Catriona McLean and Haiman, {Christopher A} and Henderson, {Brian E} and Fredrick Schumacher and {Le Marchand}, Loic and Jacques Simard and Goldberg, {Mark S} and France Labr{\`e}che and Martine Dumont and Vessela Kristensen and Aln{\ae}s, {Grethe Grenaker} and Silje Nord and Anne-Lise Borresen-Dale and Wei Zheng and Sandra Deming-Halverson and Martha Shrubsole and Jirong Long and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Andrulis, {Irene L} and Knight, {Julia A} and Gord Glendon and Sandrine Tchatchou and Peter Devilee and Tollenaar, {Robertus A E M} and Seynaeve, {Caroline M} and {Van Asperen}, {Christi J} and Montserrat Garcia-Closas and Jonine Figueroa and Chanock, {Stephen J} and Jolanta Lissowska and Kamila Czene and Hatef Darabi and Mikael Eriksson and Daniel Klevebring and Hooning, {Maartje J} and Antoinette Hollestelle and {van Deurzen}, {Carolien H M} and Mieke Kriege and Per Hall and Jingmei Li and Jianjun Liu and Keith Humphreys and Angela Cox and Cross, {Simon S} and Reed, {Malcolm W R} and Pharoah, {Paul D P} and Dunning, {Alison M} and Mitul Shah and Perkins, {Barbara J} and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Alan Ashworth and Anthony Swerdlow and Michael Jones and Schoemaker, {Minouk J} and Alfons Meindl and Schmutzler, {Rita K} and Curtis Olswold and Susan Slager and Toland, {Amanda E} and Drakoulis Yannoukakos and Kenneth Muir and Artitaya Lophatananon and Sarah Stewart-Brown and Pornthep Siriwanarangsan and Keitaro Matsuo and Hidema Ito and Hiroji Iwata and Junko Ishiguro and Wu, {Anna H} and Chiu-Chen Tseng and {Van Den Berg}, David and Stram, {Daniel O} and Teo, {Soo Hwang} and Yip, {Cheng Har} and Peter Kang and Ikram, {Mohammad Kamran} and Xiao-Ou Shu and Wei Lu and Yu-Tang Gao and Hui Cai and Daehee Kang and Ji-Yeob Choi and Park, {Sue K} and Dong-Young Noh and Mikael Hartman and Hui Miao and Lim, {Wei Yen} and Lee, {Soo Chin} and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James Mckay and Pei-Ei Wu and Ming-Feng Hou and Jyh-Cherng Yu and Chen-Yang Shen and William Blot and Qiuyin Cai and Signorello, {Lisa B} and Craig Luccarini and Caroline Bayes and Shahana Ahmed and Mel Maranian and Healey, {Catherine S} and Anna Gonz{\'a}lez-Neira and Guillermo Pita and Alonso, {M Rosario} and Nuria {\'A}lvarez and Daniel Herrero and Tessier, {Daniel C} and Daniel Vincent and Francois Bacot and Hunter, {David J} and Sara Lindstrom and Joe Dennis and Kyriaki Michailidou and Bolla, {Manjeet K} and Easton, {Douglas F} and {dos Santos Silva}, Isabel and Olivia Fletcher and Julian Peto and {GENICA Network} and Volker Harth",
note = "{\textcopyright} The Author 2015. Published by Oxford University Press.",
year = "2015",
month = may,
day = "15",
doi = "10.1093/hmg/ddv035",
language = "English",
volume = "24",
pages = "2966--84",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

AU - Orr, Nick

AU - Dudbridge, Frank

AU - Dryden, Nicola

AU - Maguire, Sarah

AU - Novo, Daniela

AU - Perrakis, Eleni

AU - Johnson, Nichola

AU - Ghoussaini, Maya

AU - Hopper, John L

AU - Southey, Melissa C

AU - Apicella, Carmel

AU - Stone, Jennifer

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Van't Veer, Laura J

AU - Hogervorst, Frans B

AU - Fasching, Peter A

AU - Haeberle, Lothar

AU - Ekici, Arif B

AU - Beckmann, Matthias W

AU - Gibson, Lorna

AU - Aitken, Zoe

AU - Warren, Helen

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael J

AU - Miller, Nicola

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Schneeweiss, Andreas

AU - Sohn, Chistof

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Cordina-Duverger, Emilie

AU - Sanchez, Marie

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G

AU - Nielsen, Sune F

AU - Flyger, Henrik

AU - Benitez, Javier

AU - Zamora, Maria Pilar

AU - Arias Perez, Jose Ignacio

AU - Menéndez, Primitiva

AU - Anton-Culver, Hoda

AU - Neuhausen, Susan L

AU - Brenner, Hermann

AU - Dieffenbach, Aida Karina

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Hamann, Ute

AU - Brauch, Hiltrud

AU - Justenhoven, Christina

AU - Brüning, Thomas

AU - Ko, Yon-Dschun

AU - Nevanlinna, Heli

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Khan, Sofia

AU - Bogdanova, Natalia

AU - Dörk, Thilo

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Hartikainen, Jaana M

AU - Chenevix-Trench, Georgia

AU - Beesley, Jonathan

AU - Lambrechts, Diether

AU - Moisse, Matthieu

AU - Floris, Guiseppe

AU - Beuselinck, Benoit

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Peissel, Bernard

AU - Pensotti, Valeria

AU - Couch, Fergus J

AU - Olson, Janet E

AU - Slettedahl, Seth

AU - Vachon, Celine

AU - Giles, Graham G

AU - Milne, Roger L

AU - McLean, Catriona

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Schumacher, Fredrick

AU - Le Marchand, Loic

AU - Simard, Jacques

AU - Goldberg, Mark S

AU - Labrèche, France

AU - Dumont, Martine

AU - Kristensen, Vessela

AU - Alnæs, Grethe Grenaker

AU - Nord, Silje

AU - Borresen-Dale, Anne-Lise

AU - Zheng, Wei

AU - Deming-Halverson, Sandra

AU - Shrubsole, Martha

AU - Long, Jirong

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Andrulis, Irene L

AU - Knight, Julia A

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Devilee, Peter

AU - Tollenaar, Robertus A E M

AU - Seynaeve, Caroline M

AU - Van Asperen, Christi J

AU - Garcia-Closas, Montserrat

AU - Figueroa, Jonine

AU - Chanock, Stephen J

AU - Lissowska, Jolanta

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Klevebring, Daniel

AU - Hooning, Maartje J

AU - Hollestelle, Antoinette

AU - van Deurzen, Carolien H M

AU - Kriege, Mieke

AU - Hall, Per

AU - Li, Jingmei

AU - Liu, Jianjun

AU - Humphreys, Keith

AU - Cox, Angela

AU - Cross, Simon S

AU - Reed, Malcolm W R

AU - Pharoah, Paul D P

AU - Dunning, Alison M

AU - Shah, Mitul

AU - Perkins, Barbara J

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Ashworth, Alan

AU - Swerdlow, Anthony

AU - Jones, Michael

AU - Schoemaker, Minouk J

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Olswold, Curtis

AU - Slager, Susan

AU - Toland, Amanda E

AU - Yannoukakos, Drakoulis

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Stewart-Brown, Sarah

AU - Siriwanarangsan, Pornthep

AU - Matsuo, Keitaro

AU - Ito, Hidema

AU - Iwata, Hiroji

AU - Ishiguro, Junko

AU - Wu, Anna H

AU - Tseng, Chiu-Chen

AU - Van Den Berg, David

AU - Stram, Daniel O

AU - Teo, Soo Hwang

AU - Yip, Cheng Har

AU - Kang, Peter

AU - Ikram, Mohammad Kamran

AU - Shu, Xiao-Ou

AU - Lu, Wei

AU - Gao, Yu-Tang

AU - Cai, Hui

AU - Kang, Daehee

AU - Choi, Ji-Yeob

AU - Park, Sue K

AU - Noh, Dong-Young

AU - Hartman, Mikael

AU - Miao, Hui

AU - Lim, Wei Yen

AU - Lee, Soo Chin

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Brennan, Paul

AU - Mckay, James

AU - Wu, Pei-Ei

AU - Hou, Ming-Feng

AU - Yu, Jyh-Cherng

AU - Shen, Chen-Yang

AU - Blot, William

AU - Cai, Qiuyin

AU - Signorello, Lisa B

AU - Luccarini, Craig

AU - Bayes, Caroline

AU - Ahmed, Shahana

AU - Maranian, Mel

AU - Healey, Catherine S

AU - González-Neira, Anna

AU - Pita, Guillermo

AU - Alonso, M Rosario

AU - Álvarez, Nuria

AU - Herrero, Daniel

AU - Tessier, Daniel C

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Hunter, David J

AU - Lindstrom, Sara

AU - Dennis, Joe

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K

AU - Easton, Douglas F

AU - dos Santos Silva, Isabel

AU - Fletcher, Olivia

AU - Peto, Julian

AU - GENICA Network

AU - Harth, Volker

N1 - © The Author 2015. Published by Oxford University Press.

PY - 2015/5/15

Y1 - 2015/5/15

N2 - We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.

AB - We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.

U2 - 10.1093/hmg/ddv035

DO - 10.1093/hmg/ddv035

M3 - SCORING: Journal article

C2 - 25652398

VL - 24

SP - 2966

EP - 2984

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 10

ER -