GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 x 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology. ; Ghoussaini, Maya Edwards, Stacey L Michailidou, Kyriaki Nord, Silje Cowper-Sal Lari, Richard Desai, Kinjal Kar, Siddhartha Hillman, Kristine M Kaufmann, Susanne Glubb, Dylan M Beesley, Jonathan Dennis, Joe Bolla, Manjeet K Wang, Qin Dicks, Ed Guo, Qi Schmidt, Marjanka K Shah, Mitul Luben, Robert Brown, Judith Czene, Kamila Darabi, Hatef Eriksson, Mikael Klevebring, Daniel Bojesen, Stig E Nordestgaard, Borge G Nielsen, Sune F Flyger, Henrik Lambrechts, Diether Thienpont, Bernard Neven, Patrick Wildiers, Hans Broeks, Annegien Van't Veer, Laura J Th Rutgers, Emiel J Couch, Fergus J Olson, Janet E Hallberg, Emily Vachon, Celine Chang-Claude, Jenny Rudolph, Anja Seibold, Petra Flesch-Janys, Dieter Peto, Julian Dos-Santos-Silva, Isabel Gibson, Lorna Nevanlinna, Heli Muranen, Taru A Aittomaki, Kristiina Blomqvist, Carl Hall, Per Li, Jingmei Liu, Jianjun Humphreys, Keith Kang, Daehee Choi, Ji-Yeob Park, Sue K Noh, Dong-Young Matsuo, Keitaro Ito, Hidemi Iwata, Hiroji Yatabe, Yasushi Guenel, Pascal Truong, Therese Menegaux, Florence Sanchez, Marie Burwinkel, Barbara Marme, Frederik Schneeweiss, Andreas Sohn, Christof Wu, Anna H Tseng, Chiu-Chen Van Den Berg, David Stram, Daniel O Benitez, Javier Zamora, M Pilar Perez, Jose Ignacio Arias Menendez, Primitiva Shu, Xiao-Ou Lu, Wei Gao, Yu-Tang Cai, Qiuyin Cox, Angela Cross, Simon S Reed, Malcolm W R Andrulis, Irene L Knight, Julia A Glendon, Gord Tchatchou, Sandrine Sawyer, Elinor J Tomlinson, Ian Kerin, Michael J Miller, Nicola Haiman, Christopher A Henderson, Brian E Schumacher, Fredrick Le Marchand, Loic Lindblom, Annika Margolin, Sara Teo, Soo Hwang Yip, Cheng Har Lee, Daphne S C Wong, Tien Y Hooning, Maartje J Martens, John W M Collee, J Margriet van Deurzen, Carolien H M Hopper, John L Southey, Melissa C Tsimiklis, Helen Kapuscinski, Miroslav K Shen, Chen-Yang Wu, Pei-Ei Yu, Jyh-Cherng Chen, Shou-Tung Alnaes, Grethe Grenaker Borresen-Dale, Anne-Lise Giles, Graham G Milne, Roger L McLean, Catriona Muir, Kenneth Lophatananon, Artitaya Stewart-Brown, Sarah Siriwanarangsan, Pornthep Hartman, Mikael Miao, Hui Buhari, Shaik Ahmad Bin Syed Teo, Yik Ying Fasching, Peter A Haeberle, Lothar Ekici, Arif B Beckmann, Matthias W Brenner, Hermann Dieffenbach, Aida Karina Arndt, Volker Stegmaier, Christa Swerdlow, Anthony Ashworth, Alan Orr, Nick Schoemaker, Minouk J Garcia-Closas, Montserrat Figueroa, Jonine Chanock, Stephen J Lissowska, Jolanta Simard, Jacques Goldberg, Mark S Labreche, France Dumont, Martine Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Brauch, Hiltrud Bruning, Thomas Koto, Yon-Dschun Radice, Paolo Peterlongo, Paolo Bonanni, Bernardo Volorio, Sara Dork, Thilo Bogdanova, Natalia V Helbig, Sonja Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana M Devilee, Peter Tollenaar, Robert A E M Seynaeve, Caroline Van Asperen, Christi J Jakubowska, Anna Lubinski, Jan Jaworska-Bieniek, Katarzyna Durda, Katarzyna Slager, Susan Toland, Amanda E Ambrosone, Christine B Yannoukakos, Drakoulis Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul McKay, James Hamann, Ute Torres, Diana Zheng, Wei Long, Jirong Anton-Culver, Hoda Neuhausen, Susan L Luccarini, Craig Baynes, Caroline Ahmed, Shahana Maranian, Mel Healey, Catherine S Gonzalez-Neira, Anna Pita, Guillermo Alonso, M Rosario Alvarez, Nuria Herrero, Daniel Tessier, Daniel C Vincent, Daniel Bacot, Francois de Santiago, Ines Carroll, Jason Caldas, Carlos Brown, Melissa A Lupien, Mathieu Kristensen, Vessela N Pharoah, Paul D P Chenevix-Trench, Georgia French, Juliet D Easton, Douglas F Dunning, Alison M Australian Ovarian Cancer Management Group 16561/Cancer Research UK/United Kingdom England Nature communications Nat Commun. 2014 Sep 23;4:4999. doi: 10.1038/ncomms5999.