Florey Department of Neuroscience and Mental Health - Research Publications

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    Common variants in breast cancer risk loci predispose to distinct tumor subtypes
    Ahearn, TU ; Zhang, H ; Michailidou, K ; Milne, RL ; Bolla, MK ; Dennis, J ; Dunning, AM ; Lush, M ; Wang, Q ; Andrulis, IL ; Anton-Culver, H ; Arndt, V ; Aronson, KJ ; Auer, PL ; Augustinsson, A ; Baten, A ; Becher, H ; Behrens, S ; Benitez, J ; Bermisheva, M ; Blomqvist, C ; Bojesen, SE ; Bonanni, B ; Borresen-Dale, A-L ; Brauch, H ; Brenner, H ; Brooks-Wilson, A ; Bruening, T ; Burwinkel, B ; Buys, SS ; Canzian, F ; Castelao, JE ; Chang-Claude, J ; Chanock, SJ ; Chenevix-Trench, G ; Clarke, CL ; Collee, JM ; Cox, A ; Cross, SS ; Czene, K ; Daly, MB ; Devilee, P ; Dork, T ; Dwek, M ; Eccles, DM ; Evans, DG ; Fasching, PA ; Figueroa, J ; Floris, G ; Gago-Dominguez, M ; Gapstur, SM ; Garcia-Saenz, JA ; Gaudet, MM ; Giles, GG ; Goldberg, MS ; Gonzalez-Neira, A ; Alnaes, GIG ; Grip, M ; Guenel, P ; Haiman, CA ; Hall, P ; Hamann, U ; Harkness, EF ; Heemskerk-Gerritsen, BAM ; Holleczek, B ; Hollestelle, A ; Hooning, MJ ; Hoover, RN ; Hopper, JL ; Howell, A ; Jakimovska, M ; Jakubowska, A ; John, EM ; Jones, ME ; Jung, A ; Kaaks, R ; Kauppila, S ; Keeman, R ; Khusnutdinova, E ; Kitahara, CM ; Ko, Y-D ; Koutros, S ; Kristensen, VN ; Kruger, U ; Kubelka-Sabit, K ; Kurian, AW ; Kyriacou, K ; Lambrechts, D ; Lee, DG ; Lindblom, A ; Linet, M ; Lissowska, J ; Llaneza, A ; Lo, W-Y ; MacInnis, RJ ; Mannermaa, A ; Manoochehri, M ; Margolin, S ; Martinez, ME ; McLean, C ; Meindl, A ; Menon, U ; Nevanlinna, H ; Newman, WG ; Nodora, J ; Offit, K ; Olsson, H ; Orr, N ; Park-Simon, T-W ; Patel, A ; Peto, J ; Pita, G ; Plaseska-Karanfilska, D ; Prentice, R ; Punie, K ; Pylkas, K ; Radice, P ; Rennert, G ; Romero, A ; Ruediger, T ; Saloustros, E ; Sampson, S ; Sandler, DP ; Sawyer, EJ ; Schmutzler, RK ; Schoemaker, MJ ; Schottker, B ; Sherman, ME ; Shu, X-O ; Smichkoska, S ; Southey, MC ; Spinelli, JJ ; Swerdlow, AJ ; Tamimi, RM ; Tapper, WJ ; Taylor, JA ; Teras, LR ; Terry, MB ; Torres, D ; Troester, MA ; Vachon, CM ; van Deurzen, CHM ; van Veen, EM ; Wagner, P ; Weinberg, CR ; Wendt, C ; Wesseling, J ; Winqvist, R ; Wolk, A ; Yang, XR ; Zheng, W ; Couch, FJ ; Simard, J ; Kraft, P ; Easton, DF ; Pharoah, PDP ; Schmidt, MK ; Garcia-Closas, M ; Chatterjee, N (BMC, 2022-01-04)
    BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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    Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
    Zhan, H ; Ahearn, TU ; Lecarpentier, J ; Barnes, D ; Beesley, J ; Qi, G ; Jiang, X ; O'Mara, TA ; Zhao, N ; Bolla, MK ; Dunning, AM ; Dennis, J ; Wang, Q ; Abu Ful, Z ; Aittomaki, K ; Andrulis, IL ; Anton-Culver, H ; Arndt, V ; Aronson, KJ ; Arun, BK ; Auer, PL ; Azzollini, J ; Barrowdale, D ; Becher, H ; Beckmann, MW ; Behrens, S ; Benitez, J ; Bermisheva, M ; Bialkowska, K ; Blanco, A ; Blomqvist, C ; Bogdanova, N ; Bojesen, SE ; Bonanni, B ; Bondavalli, D ; Borg, A ; Brauch, H ; Brenner, H ; Briceno, I ; Broeks, A ; Brucker, SY ; Bruening, T ; Burwinkel, B ; Buys, SS ; Byers, H ; Caldes, T ; Caligo, MA ; Calvello, M ; Campa, D ; Castelao, JE ; Chang-Claude, J ; Chanock, SJ ; Christiaens, M ; Christiansen, H ; Chung, WK ; Claes, KBM ; Clarke, CL ; Cornelissen, S ; Couch, FJ ; Cox, A ; Cross, SS ; Czene, K ; Daly, MB ; Devilee, P ; Diez, O ; Domchek, SM ; Doerk, T ; Dwek, M ; Eccles, DM ; Ekici, AB ; Evans, DG ; Fasching, PA ; Figueroa, J ; Foretova, L ; Fostira, F ; Friedman, E ; Frost, D ; Gago-Dominguez, M ; Gapstur, SM ; Garber, J ; Garcia-Saenz, JA ; Gaudet, MM ; Gayther, SA ; Giles, GG ; Godwin, AK ; Goldberg, MS ; Goldgar, DE ; Gonzalez-Neira, A ; Greene, MH ; Gronwald, J ; Guenel, P ; Haeberle, L ; Hahnen, E ; Haiman, CA ; Hake, CR ; Hall, P ; Hamann, U ; Harkness, EF ; Heemskerk-Gerritsen, BAM ; Hillemanns, P ; Hogervorst, FBL ; Holleczek, B ; Hollestelle, A ; Hooning, MJ ; Hoover, RN ; Hopper, JL ; Howell, A ; Huebner, H ; Hulick, PJ ; Imyanitov, EN ; Isaacs, C ; Izatt, L ; Jager, A ; Jakimovska, M ; Jakubowska, A ; James, P ; Janavicius, R ; Janni, W ; John, EM ; Jones, ME ; Jung, A ; Kaaks, R ; Kapoor, PM ; Karlan, BY ; Keeman, R ; Khan, S ; Khusnutdinova, E ; Kitahara, CM ; Ko, Y-D ; Konstantopoulou, I ; Koppert, LB ; Koutros, S ; Kristensen, VN ; Laenkholm, A-V ; Lambrechts, D ; Larsson, SC ; Laurent-Puig, P ; Lazaro, C ; Lazarova, E ; Lejbkowicz, F ; Leslie, G ; Lesueur, F ; Lindblom, A ; Lissowska, J ; Lo, W-Y ; Loud, JT ; Lubinski, J ; Lukomska, A ; MacInnis, RJ ; Mannermaa, A ; Manoochehri, M ; Manoukian, S ; Margolin, S ; Martinez, ME ; Matricardi, L ; McGuffog, L ; McLean, C ; Mebirouk, N ; Meindl, A ; Menon, U ; Miller, A ; Mingazheva, E ; Montagna, M ; Mulligan, AM ; Mulot, C ; Muranen, TA ; Nathanson, KL ; Neuhausen, SL ; Nevanlinna, H ; Neven, P ; Newman, WG ; Nielsens, FC ; Nikitina-Zake, L ; Nodora, J ; Offit, K ; Olah, E ; Olopade, O ; Olsson, H ; Orr, N ; Papi, L ; Papp, J ; Park-Simon, T-W ; Parsons, MT ; Peissel, B ; Peixoto, A ; Peshkin, B ; Peterlongo, P ; Peto, J ; Phillips, K-A ; Piedmonte, M ; Plaseska-Karanfilska, D ; Prajzendanc, K ; Prentice, R ; Prokofyeva, D ; Rack, B ; Radice, P ; Ramus, SJ ; Rantala, J ; Rashid, MU ; Rennert, G ; Rennert, HS ; Risch, HA ; Romero, A ; Rookus, MA ; Ruebner, M ; Ruediger, T ; Saloustros, E ; Sampson, S ; Sandler, DP ; Sawyer, EJ ; Scheuner, MT ; Schmutzler, RK ; Schneeweiss, A ; Schoemaker, MJ ; Schoettker, B ; Schuermann, P ; Senter, L ; Sharma, P ; Sherman, ME ; Shu, X-O ; Singer, CF ; Smichkoska, S ; Soucy, P ; Southey, MC ; Spinelli, JJ ; Stone, J ; Stoppa-Lyonnet, D ; Swerdlow, AJ ; Szabo, C ; Tamimi, RM ; Tapper, WJ ; Taylor, JA ; Teixeira, MR ; Terry, M ; Thomassen, M ; Thull, DL ; Tischkowitz, M ; Toland, AE ; Tollenaar, RAEM ; Tomlinson, I ; Torres, D ; Troester, MA ; Truong, T ; Tung, N ; Untch, M ; Vachon, CM ; van den Ouweland, AMW ; van der Kolk, LE ; van Veen, EM ; vanRensburg, EJ ; Vega, A ; Wappenschmidt, B ; Weinberg, CR ; Weitzel, JN ; Wildiers, H ; Winqvist, R ; Wolk, A ; Yang, XR ; Yannoukakos, D ; Zheng, W ; Zorn, KK ; Milne, RL ; Kraft, P ; Simard, J ; Pharoah, PDP ; Michailidou, K ; Antoniou, AC ; Schmidt, MK ; Chenevix-Trench, G ; Easton, DF ; Chatterjee, N ; Garcia-Closas, M (NATURE RESEARCH, 2020-06)
    Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
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    Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
    Fachal, L ; Aschard, H ; Beesley, J ; Barnes, DR ; Allen, J ; Kar, S ; Pooley, KA ; Dennis, J ; Michailidou, K ; Turman, C ; Soucy, P ; Lemacon, A ; Lush, M ; Tyrer, JP ; Ghoussaini, M ; Marjaneh, MM ; Jiang, X ; Agata, S ; Aittomaki, K ; Rosario Alonso, M ; Andrulis, IL ; Anton-Culver, H ; Antonenkova, NN ; Arason, A ; Arndt, V ; Aronson, KJ ; Arun, BK ; Auber, B ; Auer, PL ; Azzollini, J ; Balmana, J ; Barkardottir, RB ; Barrowdale, D ; Beeghly-Fadiel, A ; Benitez, J ; Bermisheva, M ; Bialkowska, K ; Blanco, AM ; Blomqvist, C ; Blot, W ; Bogdanova, N ; Bojesen, SE ; Bolla, MK ; Bonanni, B ; Borg, A ; Bosse, K ; Brauch, H ; Brenner, H ; Briceno, I ; Brock, IW ; Brooks-Wilson, A ; Bruening, T ; Burwinkel, B ; Buys, SS ; Cai, Q ; Caldes, T ; Caligo, MA ; Camp, NJ ; Campbell, I ; Canzian, F ; Carroll, JS ; Carter, BD ; Castelao, JE ; Chiquette, J ; Christiansen, H ; Chung, WK ; Claes, KBM ; Clarke, CL ; Collee, JM ; Cornelissen, S ; Couch, FJ ; Cox, A ; Cross, SS ; Cybulski, C ; Czene, K ; Daly, MB ; de la Hoya, M ; Devilee, P ; Diez, O ; Ding, YC ; Dite, GS ; Domchek, SM ; Doerk, T ; dos-Santos-Silva, I ; Droit, A ; Dubois, S ; Dumont, M ; Duran, M ; Durcan, L ; Dwek, M ; Eccles, DM ; Engel, C ; Eriksson, M ; Evans, DG ; Fasching, PA ; Fletcher, O ; Floris, G ; Flyger, H ; Foretova, L ; Foulkes, WD ; Friedman, E ; Fritschi, L ; Frost, D ; Gabrielson, M ; Gago-Dominguez, M ; Gambino, G ; Ganz, PA ; Gapstur, SM ; Garber, J ; Garcia-Saenz, JA ; Gaudet, MM ; Georgoulias, V ; Giles, GG ; Glendon, G ; Godwin, AK ; Goldberg, MS ; Goldgar, DE ; Gonzalez-Neira, A ; Tibiletti, MG ; Greene, MH ; Grip, M ; Gronwald, J ; Grundy, A ; Guenel, P ; Hahnen, E ; Haiman, CA ; Hakansson, N ; Hall, P ; Hamann, U ; Harrington, PA ; Hartikainen, JM ; Hartman, M ; He, W ; Healey, CS ; Heemskerk-Gerritsen, BAM ; Heyworth, J ; Hillemanns, P ; Hogervorst, FBL ; Hollestelle, A ; Hooning, MJ ; Hopper, JL ; Howell, A ; Huang, G ; Hulick, PJ ; Imyanitov, EN ; Isaacs, C ; Iwasaki, M ; Jager, A ; Jakimovska, M ; Jakubowska, A ; James, PA ; Janavicius, R ; Jankowitz, RC ; John, EM ; Johnson, N ; Jones, ME ; Jukkola-Vuorinen, A ; Jung, A ; Kaaks, R ; Kang, D ; Kapoor, PM ; Karlan, BY ; Keeman, R ; Kerin, MJ ; Khusnutdinova, E ; Kiiski, J ; Kirk, J ; Kitahara, CM ; Ko, Y-D ; Konstantopoulou, I ; Kosma, V-M ; Koutros, S ; Kubelka-Sabit, K ; Kwong, A ; Kyriacou, K ; Laitman, Y ; Lambrechts, D ; Lee, E ; Leslie, G ; Lester, J ; Lesueur, F ; Lindblom, A ; Lo, W-Y ; Long, J ; Lophatananon, A ; Loud, JT ; Lubinski, J ; MacInnis, RJ ; Maishman, T ; Makalic, E ; Mannermaa, A ; Manoochehri, M ; Manoukian, S ; Margolin, S ; Martinez, ME ; Matsuo, K ; Maurer, T ; Mavroudis, D ; Mayes, R ; McGuffog, L ; McLean, C ; Mebirouk, N ; Meindl, A ; Miller, A ; Miller, N ; Montagna, M ; Moreno, F ; Muir, K ; Mulligan, AM ; Munoz-Garzon, VM ; Muranen, TA ; Narod, SA ; Nassir, R ; Nathanson, KL ; Neuhausen, SL ; Nevanlinna, H ; Neven, P ; Nielsen, FC ; Nikitina-Zake, L ; Norman, A ; Offit, K ; Olah, E ; Olopade, O ; Olsson, H ; Orr, N ; Osorio, A ; Pankratz, VS ; Papp, J ; Park, SK ; Park-Simon, T-W ; Parsons, MT ; Paul, J ; Pedersen, IS ; Peissel, B ; Peshkin, B ; Peterlongo, P ; Peto, J ; Plaseska-Karanfilska, D ; Prajzendanc, K ; Prentice, R ; Presneau, N ; Prokofyeva, D ; Angel Pujana, M ; Pylkas, K ; Radice, P ; Ramus, SJ ; Rantala, J ; Rau-Murthy, R ; Rennert, G ; Risch, HA ; Robson, M ; Romero, A ; Rossing, M ; Saloustros, E ; Sanchez-Herrero, E ; Sandler, DP ; Santamarina, M ; Saunders, C ; Sawyer, EJ ; Scheuner, MT ; Schmidt, DF ; Schmutzler, RK ; Schneeweiss, A ; Schoemaker, MJ ; Schoettker, B ; Schuermann, P ; Scott, C ; Scott, RJ ; Senter, L ; Seynaeve, CM ; Shah, M ; Sharma, P ; Shen, C-Y ; Shu, X-O ; Singer, CF ; Slavin, TP ; Smichkoska, S ; Southey, MC ; Spinelli, JJ ; Spurdle, AB ; Stone, J ; Stoppa-Lyonnet, D ; Sutter, C ; Swerdlow, AJ ; Tamimi, RM ; Tan, YY ; Tapper, WJ ; Taylor, JA ; Teixeira, MR ; Tengstroem, M ; Teo, SH ; Terry, MB ; Teul, A ; Thomassen, M ; Thull, DL ; Tischkowitz, M ; Toland, AE ; Tollenaar, RAEM ; Tomlinson, I ; Torres, D ; Torres-Mejia, G ; Troester, MA ; Truong, T ; Tung, N ; Tzardi, M ; Ulmer, H-U ; Vachon, CM ; van Asperen, CJ ; van der Kolk, LE ; van Rensburg, EJ ; Vega, A ; Viel, A ; Vijai, J ; Vogel, MJ ; Wang, Q ; Wappenschmidt, B ; Weinberg, CR ; Weitzel, JN ; Wendt, C ; Wildiers, H ; Winqvist, R ; Wolk, A ; Wu, AH ; Yannoukakos, D ; Zhang, Y ; Zheng, W ; Hunter, D ; Pharoah, PDP ; Chang-Claude, J ; Garcia-Closas, M ; Schmidt, MK ; Milne, RL ; Kristensen, VN ; French, JD ; Edwards, SL ; Antoniou, AC ; Chenevix-Trench, G ; Simard, J ; Easton, DF ; Kraft, P ; Dunning, AM ; Mari, V ; Berthet, P ; Castera, L ; Vaur, D ; Lallaoui, H ; Bignon, Y-J ; Uhrhammer, N ; Bonadona, V ; Lasset, C ; Revillion, F ; Vennin, P ; Muller, D ; Gomes, DM ; Ingster, O ; Coupier, I ; Pujol, P ; Collonge-Rame, M-A ; Mortemousque, I ; Bera, O ; Rose, M ; Baurand, A ; Bertolone, G ; Faivre, L ; Dreyfus, H ; Leroux, D ; Venat-Bouvet, L ; Bezieau, S ; Delnatte, C ; Chiesa, J ; Gilbert-Dussardier, B ; Gesta, P ; Prieur, FP ; Bronner, M ; Sokolowska, J ; Coulet, F ; Boutry-Kryza, N ; Calender, A ; Giraud, S ; Leone, M ; Fert-Ferrer, S ; Jiao, Y ; Lesueur, FL ; Barouk-Simonet, E ; Bubien, V ; Longy, M ; Sevenet, N ; Gladieff, L ; Toulas, C ; Reimineras, A ; Sobol, H ; Bressac-de Paillerets, B ; Cabaret, O ; Caron, O ; Guillaud-Bataille, M ; Rouleau, E ; Belotti, M ; Buecher, B ; Caputo, S ; Colas, C ; De Pauw, A ; Fourme, E ; Gauthier-Villars, M ; Golmard, L ; Moncoutier, V ; Saule, C ; Donaldson, A ; Murray, A ; Brady, A ; Brewer, C ; Pottinger, C ; Miller, C ; Gallagher, D ; Gregory, H ; Cook, J ; Eason, J ; Adlard, J ; Barwell, J ; Ong, K-R ; Snape, K ; Walker, L ; Izatt, L ; Side, L ; Rogers, MT ; Porteous, ME ; Ahmed, M ; Morrison, PJ ; Brennan, P ; Eeles, R ; Davidson, R ; Sexton, A ; Christian, A ; Trainer, A ; Spigelman, A ; Fellows, A ; Shelling, A ; De Fazio, A ; Blackburn, A ; Crook, A ; Meiser, B ; Patterson, B ; Clarke, C ; Hunt, C ; Scott, C ; Amor, D ; Marsh, D ; Edkins, E ; Salisbury, E ; Haan, E ; Neidermayr, E ; Macrea, F ; Farshid, G ; Lindeman, G ; Trench, G ; Mann, G ; Giles, G ; Gill, G ; Thorne, H ; Hickie, I ; Winship, I ; Flanagan, J ; Kollias, J ; Visvader, J ; Taylor, J ; Burke, J ; Saunus, J ; Forbes, J ; Hopper, J ; French, J ; Tucker, K ; Wu, K ; Phillips, K ; Lipton, L ; Andrews, L ; Lobb, L ; Walker, L ; Kentwell, M ; Spurdle, M ; Cummings, M ; Gleeson, M ; Harris, M ; Jenkins, M ; Young, MA ; Delatycki, M ; Wallis, M ; Burgess, M ; Price, M ; Brown, M ; Southey, M ; Bogwitz, M ; Field, M ; Friedlander, M ; Gattas, M ; Saleh, M ; Hayward, N ; Pachter, N ; Cohen, P ; Duijf, P ; James, P ; Simpson, P ; Fong, P ; Butow, P ; Williams, R ; Kefford, R ; Scott, R ; Milne, R ; Balleine, R ; Dawson, S ; Lok, S ; O'Connell, S ; Greening, S ; Nightingale, S ; Edwards, S ; Fox, S ; Mclachlan, S-A ; Lakhani, S ; Antill, Y ; Aalfs, C ; Meijers-Heijboer, H ; van Engelen, K ; Gille, H ; Boere, I ; Collee, M ; van Deurzen, C ; Hooning, M ; Obdeijn, I-M ; van den Ouweland, A ; Seynaeve, C ; Siesling, S ; Verloop, J ; van Asperen, C ; van Cronenburg, T ; Blok, R ; de Boer, M ; Garcia, EG ; Adank, M ; Hogervorst, F ; Jenner, D ; van Leeuwen, F ; Rookus, M ; Russell, N ; Schmidt, M ; van den Belt-Dusebout, S ; Kets, C ; Mensenkamp, A ; de Bock, T ; van Der Hout, A ; Mourits, M ; Oosterwijk, J ; Ausems, M ; Koudijs, M ; Marsh, D ; Baxter, R ; Yip, D ; Carpenter, J ; Davis, A ; Pathmanathan, N ; Simpson, P ; Graham, D ; Sachchithananthan, M (NATURE RESEARCH, 2020-01-07)
    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.