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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Manuel Ferreira 1 Eric Gamazon 2, 3 Fares Al-Ejeh 1 Kristiina Aittomäki 4 Irene Andrulis 5 Hoda Anton-Culver 6 Adalgeir Arason 7 Volker Arndt 8 Kristan Aronson 9 Banu Arun 10 Ella Asseryanis 11 Jacopo Azzollini 12 Judith Balmaña 13 Daniel Barnes 3 Daniel Barrowdale 14 Matthias Beckmann 15 Sabine Behrens 8 Javier Benitez 16, 17 Marina Bermisheva 18 Katarzyna Białkowska 19 Carl Blomqvist 20, 4 Natalia Bogdanova 21, 22 Stig Bojesen 23 Manjeet Bolla 24 Åke Borg 25 Hiltrud Brauch 26, 27 Hermann Brenner 28 Annegien Broeks 29 Barbara Burwinkel 30, 31 Trinidad Caldés 32 Maria Caligo 33 Daniele Campa 33, 8 Ian Campbell 34 Federico Canzian 8 Jonathan Carter 35 Brian Carter 36 Jose Castelao 37 Jenny Chang-Claude 38, 8 Stephen Chanock 39 Hans Christiansen 40 Wendy Chung 41 Kathleen Claes 42 Christine Clarke 43 Fergus Couch 44 Angela Cox 45 Simon Cross 45 Kamila Czene 46 Mary Daly 47 Miguel de la Hoya 32 Joe Dennis 24 Peter Devilee 48 Orland Diez 13 Thilo Dörk 21 Alison Dunning 3 Miriam Dwek 49 Bent Ejlertsen 50 Carolina Ellberg 51 Christoph Engel 52 Mikael Eriksson 53 Peter Fasching 54 Olivia Fletcher 55 Henrik Flyger 56 Eitan Friedman 57, 58 Debra Frost 24 Marike Gabrielson 53 Manuela Gago-Dominguez 59 Patricia Ganz 60 Susan Gapstur 36 Judy Garber 61 Montserrat García-Closas 39 José García-Sáenz 32 Mia Gaudet 36 Graham Giles 62 Gord Glendon 5 Andrew Godwin 63 Mark Goldberg 64 David Goldgar 65 Anna González-Neira 17 Mark Greene 39 Jacek Gronwald 19 Pascal Guénel 66 Christopher Haiman 67 Per Hall 46 Ute Hamann 28 Wei He 53 Jane Heyworth 68 Frans Hogervorst 69 Antoinette Hollestelle 70 Robert Hoover 71 John Hopper 72 Peter Hulick 73, 74 Keith Humphreys 53 Evgeny Imyanitov 75 Claudine Isaacs 76 Milena Jakimovska 77 Anna Jakubowska 19 Paul James 78 Ramunas Janavicius 79 Rachel Jankowitz 80 Esther John 81 Nichola Johnson 82 Vijai Joseph 83 Beth Karlan 54 Elza Khusnutdinova 84 Johanna Kiiski 4 Yon-Dschun Ko 85 Michael Jones 55 Irene Konstantopoulou 86 Vessela Kristensen 87 Yael Laitman 58 Diether Lambrechts 88 Conxi Lázaro 89 Goska Leslie 24 Jenny Lester 54 Fabienne Lesueur 90 Sara Lindström 91 Jirong Long 2 Jennifer Loud 39 Jan Lubiński 19 Enes Makalic 72 Arto Mannermaa 92 Mehdi Manoochehri 8 Sara Margolin 53 Tabea Maurer 38 Dimitrios Mavroudis 93 Lesley Mcguffog 24 Alfons Meindl 94 Usha Menon 95 Kyriaki Michailidou 96 Austin Miller 97 Marco Montagna 98 Fernando Moreno 32 Lidia Moserle 99 Anna Marie Mulligan 5 Katherine Nathanson 100 Susan Neuhausen 101 Heli Nevanlinna 4 Ines Nevelsteen 102 Finn Nielsen 50 Liene Nikitina-Zake 103 Robert Nussbaum 83 Kenneth Offit 83 Edith Olah 104 Olufunmilayo Olopade 105 Håkan Olsson 106 Ana Osorio 17, 16 Janos Papp 104 Tjoung-Won Park-Simon 40 Michael Parsons 1 Inge Søkilde Pedersen 107 Ana Peixoto 104 Paolo Peterlongo 108 Paul Pharoah 3 Dijana Plaseska-Karanfilska 77 Bruce Poppe 109 Nadege Presneau 49 Paolo Radice 110 Johanna Rantala 53 Gad Rennert 111 Harvey Risch 112 Emmanouil Saloustros 113 Kristin Sanden 114 Elinor Sawyer 115 Marjanka Schmidt 69 Rita Schmutzler 116 Priyanka Sharma 63 Xiao-Ou Shu 2 Jacques Simard 117 Christian Singer 11 Penny Soucy 117 Melissa Southey 118, 72 John Spinelli 119 Amanda Spurdle 1 Jennifer Stone 120, 72 Anthony Swerdlow 55 William Tapper 121 Jack Taylor 122 Manuel Teixeira 123, 124 Mary Beth Terry 125 Alex Teulé 89 Mads Thomassen 126 Kathrin Thöne 38 Darcy Thull 80 Marc Tischkowitz 127, 24 Amanda Toland 128 Diana Torres 129, 28 Thérèse Truong 66 Nadine Tung 130 Celine Vachon 131 Christi van Asperen 132 Ans van den Ouweland 70 Elizabeth van Rensburg 133 Ana Vega 134 Alessandra Viel 135 Qin Wang 24 Barbara Wappenschmidt 136 Jeffrey Weitzel 137 Camilla Wendt 53 Robert Winqvist 138 Xiaohong Yang 39 Drakoulis Yannoukakos 139 Argyrios Ziogas 140 Peter Kraft 141 Antonis Antoniou 24 Wei Zheng 2 Douglas Easton 142 Roger Milne 118 Jonathan Beesley 1 Georgia Chenevix-Trench 1 Pascal Pujol 143
30 Molecular Epidemiology Research Group
DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
Abstract : Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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https://hal.umontpellier.fr/hal-02863912
Contributeur : Nathalie Salvy-Cordoba <>
Soumis le : mercredi 10 juin 2020 - 17:03:01
Dernière modification le : vendredi 9 avril 2021 - 09:40:05

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Manuel Ferreira, Eric Gamazon, Fares Al-Ejeh, Kristiina Aittomäki, Irene Andrulis, et al.. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nature Communications, Nature Publishing Group, 2019, 10 (1), ⟨10.1038/s41467-018-08053-5⟩. ⟨hal-02863912⟩

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