A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Yingchang Lu; Alicia Beeghly-Fadiel; Lang Wu; Xingyi Guo; Bingshan Li; Joellen M Schildkraut; Hae Kyung Im; Yian A Chen; Jennifer B Permuth; Brett M Reid; Jamie K Teer; Kirsten B Moysich; Irene L Andrulis; Hoda Anton-Culver; Banu K Arun; Elisa V Bandera; Rosa B Barkardottir; Daniel R Barnes; Javier Benitez; Line Bjorge; James Brenton; Ralf Butzow; Trinidad Caldes; Maria A Caligo; Ian Campbell; Jenny Chang-Claude; Kathleen B M Claes; Fergus J Couch; Daniel W Cramer; Mary B Daly; Anna deFazio; Joe Dennis; Orland Diez; Susan M Domchek; Thilo Dörk; Douglas F Easton; Diana M Eccles; Peter A Fasching; Renée T Fortner; George Fountzilas; Eitan Friedman; Patricia A Ganz; Judy Garber; Graham G Giles; Andrew K Godwin; David E Goldgar; Marc T Goodman; Mark H Greene; Jacek Gronwald; Ute Hamann; Florian Heitz; Michelle A T Hildebrandt; Claus K Høgdall; Antoinette Hollestelle; Peter J Hulick; David G Huntsman; Evgeny N Imyanitov; Claudine Isaacs; Anna Jakubowska; Paul James; Beth Y Karlan; Linda E Kelemen; Lambertus A Kiemeney; Susanne K Kjaer; Ava Kwong; Nhu D Le; Goska Leslie; Fabienne Lesueur; Douglas A Levine; Amalia Mattiello; Taymaa May; Lesley McGuffog; Iain A McNeish; Melissa A Merritt; Francesmary Modugno; Marco Montagna; Susan L Neuhausen; Heli Nevanlinna; Finn C Nielsen; Liene Nikitina-Zake; Robert L Nussbaum; Kenneth Offit; Edith Olah; Olufunmilayo I Olopade; Sara H Olson; Håkan Olsson; Ana Osorio; Sue K Park; Michael T Parsons; Petra H M Peeters; Tanja Pejovic; Paolo Peterlongo; Catherine M Phelan; Miquel Angel Pujana; Susan J Ramus; Gad Rennert; Harvey Risch; Gustavo C Rodriguez; Cristina Rodríguez-Antona; Isabelle Romieu; Matti A Rookus; Mary Anne Rossing; Iwona K Rzepecka; Dale P Sandler; Rita K Schmutzler; Veronica W Setiawan; Priyanka Sharma; Weiva Sieh; Jacques Simard; Christian F Singer; Honglin Song; Melissa C Southey; Amanda B Spurdle; Rebecca Sutphen; Anthony J Swerdlow; Manuel R Teixeira; Soo H Teo; Mads Thomassen; Marc Tischkowitz; Amanda E Toland; Antonia Trichopoulou; Nadine Tung; Shelley S Tworoger; Elizabeth J van Rensburg; Adriaan Vanderstichele; Ana Vega; Digna Velez Edwards; Penelope M Webb; Jeffrey N Weitzel; Nicolas Wentzensen; Emily White; Alicja Wolk; Anna H Wu; Drakoulis Yannoukakos; Kristin K Zorn; Simon A Gayther; Antonis C Antoniou; Andrew Berchuck; Ellen L Goode; Georgia Chenevix-Trench; Thomas A Sellers; Paul D P Pharoah; Wei Zheng; Jirong Long

doi:10.1158/0008-5472.CAN-18-0951

A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Yingchang Lu, Alicia Beeghly-Fadiel, Lang Wu, Xingyi Guo, Bingshan Li, Joellen M Schildkraut, Hae Kyung Im, Yian A Chen, Jennifer B Permuth, Brett M Reid, Jamie K Teer, Kirsten B Moysich, Irene L Andrulis, Hoda Anton-Culver, Banu K Arun, Elisa V Bandera, Rosa B Barkardottir, Daniel R Barnes, Javier Benitez, Line BjorgeJames Brenton, Ralf Butzow, Trinidad Caldes, Maria A Caligo, Ian Campbell, Jenny Chang-Claude, Kathleen B M Claes, Fergus J Couch, Daniel W Cramer, Mary B Daly, Anna deFazio, Joe Dennis, Orland Diez, Susan M Domchek, Thilo Dörk, Douglas F Easton, Diana M Eccles, Peter A Fasching, Renée T Fortner, George Fountzilas, Eitan Friedman, Patricia A Ganz, Judy Garber, Graham G Giles, Andrew K Godwin, David E Goldgar, Marc T Goodman, Mark H Greene, Jacek Gronwald, Ute Hamann, Florian Heitz, Michelle A T Hildebrandt, Claus K Høgdall, Antoinette Hollestelle, Peter J Hulick, David G Huntsman, Evgeny N Imyanitov, Claudine Isaacs, Anna Jakubowska, Paul James, Beth Y Karlan, Linda E Kelemen, Lambertus A Kiemeney, Susanne K Kjaer, Ava Kwong, Nhu D Le, Goska Leslie, Fabienne Lesueur, Douglas A Levine, Amalia Mattiello, Taymaa May, Lesley McGuffog, Iain A McNeish, Melissa A Merritt, Francesmary Modugno, Marco Montagna, Susan L Neuhausen, Heli Nevanlinna, Finn C Nielsen, Liene Nikitina-Zake, Robert L Nussbaum, Kenneth Offit, Edith Olah, Olufunmilayo I Olopade, Sara H Olson, Håkan Olsson, Ana Osorio, Sue K Park, Michael T Parsons, Petra H M Peeters, Tanja Pejovic, Paolo Peterlongo, Catherine M Phelan, Miquel Angel Pujana, Susan J Ramus, Gad Rennert, Harvey Risch, Gustavo C Rodriguez, Cristina Rodríguez-Antona, Isabelle Romieu, Matti A Rookus, Mary Anne Rossing, Iwona K Rzepecka, Dale P Sandler, Rita K Schmutzler, Veronica W Setiawan, Priyanka Sharma, Weiva Sieh, Jacques Simard, Christian F Singer, Honglin Song, Melissa C Southey, Amanda B Spurdle, Rebecca Sutphen, Anthony J Swerdlow, Manuel R Teixeira, Soo H Teo, Mads Thomassen, Marc Tischkowitz, Amanda E Toland, Antonia Trichopoulou, Nadine Tung, Shelley S Tworoger, Elizabeth J van Rensburg, Adriaan Vanderstichele, Ana Vega, Digna Velez Edwards, Penelope M Webb, Jeffrey N Weitzel, Nicolas Wentzensen, Emily White, Alicja Wolk, Anna H Wu, Drakoulis Yannoukakos, Kristin K Zorn, Simon A Gayther, Antonis C Antoniou, Andrew Berchuck, Ellen L Goode, Georgia Chenevix-Trench, Thomas A Sellers, Paul D P Pharoah, Wei Zheng, Jirong Long

Landspitali - The National University Hospital of Iceland

Landspitali - The National University Hospital of Iceland, Iceland

Research output: Contribution to journal › Article › peer-review

Abstract

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their

Original language	English
Journal	Cancer Research
DOIs	https://doi.org/10.1158/0008-5472.CAN-18-0951
Publication status	Published - 15 Sept 2018

Other keywords

Eggjastokkar
Krabbamein
Gen
Ovarian Neoplasms
Genome-Wide Association Study

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1158/0008-5472.CAN-18-0951

http://cancerres.aacrjournals.org/content/78/18/5419

Cite this

Lu, Y., Beeghly-Fadiel, A., Wu, L., Guo, X., Li, B., Schildkraut, J. M., Im, H. K., Chen, Y. A., Permuth, J. B., Reid, B. M., Teer, J. K., Moysich, K. B., Andrulis, I. L., Anton-Culver, H., Arun, B. K., Bandera, E. V., Barkardottir, R. B., Barnes, D. R., Benitez, J., ... Long, J. (2018). A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-18-0951

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title = "A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk",

abstract = "Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their",

keywords = "Eggjastokkar, Krabbamein, Gen, Ovarian Neoplasms, Genome-Wide Association Study, Eggjastokkar, Krabbamein, Gen, Ovarian Neoplasms, Genome-Wide Association Study",

author = "Yingchang Lu and Alicia Beeghly-Fadiel and Lang Wu and Xingyi Guo and Bingshan Li and Schildkraut, {Joellen M} and Im, {Hae Kyung} and Chen, {Yian A} and Permuth, {Jennifer B} and Reid, {Brett M} and Teer, {Jamie K} and Moysich, {Kirsten B} and Andrulis, {Irene L} and Hoda Anton-Culver and Arun, {Banu K} and Bandera, {Elisa V} and Barkardottir, {Rosa B} and Barnes, {Daniel R} and Javier Benitez and Line Bjorge and James Brenton and Ralf Butzow and Trinidad Caldes and Caligo, {Maria A} and Ian Campbell and Jenny Chang-Claude and Claes, {Kathleen B M} and Couch, {Fergus J} and Cramer, {Daniel W} and Daly, {Mary B} and Anna deFazio and Joe Dennis and Orland Diez and Domchek, {Susan M} and Thilo D{\"o}rk and Easton, {Douglas F} and Eccles, {Diana M} and Fasching, {Peter A} and Fortner, {Ren{\'e}e T} and George Fountzilas and Eitan Friedman and Ganz, {Patricia A} and Judy Garber and Giles, {Graham G} and Godwin, {Andrew K} and Goldgar, {David E} and Goodman, {Marc T} and Greene, {Mark H} and Jacek Gronwald and Ute Hamann and Florian Heitz and Hildebrandt, {Michelle A T} and H{\o}gdall, {Claus K} and Antoinette Hollestelle and Hulick, {Peter J} and Huntsman, {David G} and Imyanitov, {Evgeny N} and Claudine Isaacs and Anna Jakubowska and Paul James and Karlan, {Beth Y} and Kelemen, {Linda E} and Kiemeney, {Lambertus A} and Kjaer, {Susanne K} and Ava Kwong and Le, {Nhu D} and Goska Leslie and Fabienne Lesueur and Levine, {Douglas A} and Amalia Mattiello and Taymaa May and Lesley McGuffog and McNeish, {Iain A} and Merritt, {Melissa A} and Francesmary Modugno and Marco Montagna and Neuhausen, {Susan L} and Heli Nevanlinna and Nielsen, {Finn C} and Liene Nikitina-Zake and Nussbaum, {Robert L} and Kenneth Offit and Edith Olah and Olopade, {Olufunmilayo I} and Olson, {Sara H} and H{\aa}kan Olsson and Ana Osorio and Park, {Sue K} and Parsons, {Michael T} and Peeters, {Petra H M} and Tanja Pejovic and Paolo Peterlongo and Phelan, {Catherine M} and Pujana, {Miquel Angel} and Ramus, {Susan J} and Gad Rennert and Harvey Risch and Rodriguez, {Gustavo C} and Cristina Rodr{\'i}guez-Antona and Isabelle Romieu and Rookus, {Matti A} and Rossing, {Mary Anne} and Rzepecka, {Iwona K} and Sandler, {Dale P} and Schmutzler, {Rita K} and Setiawan, {Veronica W} and Priyanka Sharma and Weiva Sieh and Jacques Simard and Singer, {Christian F} and Honglin Song and Southey, {Melissa C} and Spurdle, {Amanda B} and Rebecca Sutphen and Swerdlow, {Anthony J} and Teixeira, {Manuel R} and Teo, {Soo H} and Mads Thomassen and Marc Tischkowitz and Toland, {Amanda E} and Antonia Trichopoulou and Nadine Tung and Tworoger, {Shelley S} and {van Rensburg}, {Elizabeth J} and Adriaan Vanderstichele and Ana Vega and Edwards, {Digna Velez} and Webb, {Penelope M} and Weitzel, {Jeffrey N} and Nicolas Wentzensen and Emily White and Alicja Wolk and Wu, {Anna H} and Drakoulis Yannoukakos and Zorn, {Kristin K} and Gayther, {Simon A} and Antoniou, {Antonis C} and Andrew Berchuck and Goode, {Ellen L} and Georgia Chenevix-Trench and Sellers, {Thomas A} and Pharoah, {Paul D P} and Wei Zheng and Jirong Long",

year = "2018",

month = sep,

day = "15",

doi = "10.1158/0008-5472.CAN-18-0951",

language = "English",

journal = "Cancer Research",

issn = "1538-7445",

publisher = "American Association for Cancer Research Inc.",

}

Lu, Y, Beeghly-Fadiel, A, Wu, L, Guo, X, Li, B, Schildkraut, JM, Im, HK, Chen, YA, Permuth, JB, Reid, BM, Teer, JK, Moysich, KB, Andrulis, IL, Anton-Culver, H, Arun, BK, Bandera, EV, Barkardottir, RB, Barnes, DR, Benitez, J, Bjorge, L, Brenton, J, Butzow, R, Caldes, T, Caligo, MA, Campbell, I, Chang-Claude, J, Claes, KBM, Couch, FJ, Cramer, DW, Daly, MB, deFazio, A, Dennis, J, Diez, O, Domchek, SM, Dörk, T, Easton, DF, Eccles, DM, Fasching, PA, Fortner, RT, Fountzilas, G, Friedman, E, Ganz, PA, Garber, J, Giles, GG, Godwin, AK, Goldgar, DE, Goodman, MT, Greene, MH, Gronwald, J, Hamann, U, Heitz, F, Hildebrandt, MAT, Høgdall, CK, Hollestelle, A, Hulick, PJ, Huntsman, DG, Imyanitov, EN, Isaacs, C, Jakubowska, A, James, P, Karlan, BY, Kelemen, LE, Kiemeney, LA, Kjaer, SK, Kwong, A, Le, ND, Leslie, G, Lesueur, F, Levine, DA, Mattiello, A, May, T, McGuffog, L, McNeish, IA, Merritt, MA, Modugno, F, Montagna, M, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, Nikitina-Zake, L, Nussbaum, RL, Offit, K, Olah, E, Olopade, OI, Olson, SH, Olsson, H, Osorio, A, Park, SK, Parsons, MT, Peeters, PHM, Pejovic, T, Peterlongo, P, Phelan, CM, Pujana, MA, Ramus, SJ, Rennert, G, Risch, H, Rodriguez, GC, Rodríguez-Antona, C, Romieu, I, Rookus, MA, Rossing, MA, Rzepecka, IK, Sandler, DP, Schmutzler, RK, Setiawan, VW, Sharma, P, Sieh, W, Simard, J, Singer, CF, Song, H, Southey, MC, Spurdle, AB, Sutphen, R, Swerdlow, AJ, Teixeira, MR, Teo, SH, Thomassen, M, Tischkowitz, M, Toland, AE, Trichopoulou, A, Tung, N, Tworoger, SS, van Rensburg, EJ, Vanderstichele, A, Vega, A, Edwards, DV, Webb, PM, Weitzel, JN, Wentzensen, N, White, E, Wolk, A, Wu, AH, Yannoukakos, D, Zorn, KK, Gayther, SA, Antoniou, AC, Berchuck, A, Goode, EL, Chenevix-Trench, G, Sellers, TA, Pharoah, PDP, Zheng, W & Long, J 2018, 'A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk', Cancer Research. https://doi.org/10.1158/0008-5472.CAN-18-0951

TY - JOUR

T1 - A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

AU - Lu, Yingchang

AU - Beeghly-Fadiel, Alicia

AU - Wu, Lang

AU - Guo, Xingyi

AU - Li, Bingshan

AU - Schildkraut, Joellen M

AU - Im, Hae Kyung

AU - Chen, Yian A

AU - Permuth, Jennifer B

AU - Reid, Brett M

AU - Teer, Jamie K

AU - Moysich, Kirsten B

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Arun, Banu K

AU - Bandera, Elisa V

AU - Barkardottir, Rosa B

AU - Barnes, Daniel R

AU - Benitez, Javier

AU - Bjorge, Line

AU - Brenton, James

AU - Butzow, Ralf

AU - Caldes, Trinidad

AU - Caligo, Maria A

AU - Campbell, Ian

AU - Chang-Claude, Jenny

AU - Claes, Kathleen B M

AU - Couch, Fergus J

AU - Cramer, Daniel W

AU - Daly, Mary B

AU - deFazio, Anna

AU - Dennis, Joe

AU - Diez, Orland

AU - Domchek, Susan M

AU - Dörk, Thilo

AU - Easton, Douglas F

AU - Eccles, Diana M

AU - Fasching, Peter A

AU - Fortner, Renée T

AU - Fountzilas, George

AU - Friedman, Eitan

AU - Ganz, Patricia A

AU - Garber, Judy

AU - Giles, Graham G

AU - Godwin, Andrew K

AU - Goldgar, David E

AU - Goodman, Marc T

AU - Greene, Mark H

AU - Gronwald, Jacek

AU - Hamann, Ute

AU - Heitz, Florian

AU - Hildebrandt, Michelle A T

AU - Høgdall, Claus K

AU - Hollestelle, Antoinette

AU - Hulick, Peter J

AU - Huntsman, David G

AU - Imyanitov, Evgeny N

AU - Isaacs, Claudine

AU - Jakubowska, Anna

AU - James, Paul

AU - Karlan, Beth Y

AU - Kelemen, Linda E

AU - Kiemeney, Lambertus A

AU - Kjaer, Susanne K

AU - Kwong, Ava

AU - Le, Nhu D

AU - Leslie, Goska

AU - Lesueur, Fabienne

AU - Levine, Douglas A

AU - Mattiello, Amalia

AU - May, Taymaa

AU - McGuffog, Lesley

AU - McNeish, Iain A

AU - Merritt, Melissa A

AU - Modugno, Francesmary

AU - Montagna, Marco

AU - Neuhausen, Susan L

AU - Nevanlinna, Heli

AU - Nielsen, Finn C

AU - Nikitina-Zake, Liene

AU - Nussbaum, Robert L

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I

AU - Olson, Sara H

AU - Olsson, Håkan

AU - Osorio, Ana

AU - Park, Sue K

AU - Parsons, Michael T

AU - Peeters, Petra H M

AU - Pejovic, Tanja

AU - Peterlongo, Paolo

AU - Phelan, Catherine M

AU - Pujana, Miquel Angel

AU - Ramus, Susan J

AU - Rennert, Gad

AU - Risch, Harvey

AU - Rodriguez, Gustavo C

AU - Rodríguez-Antona, Cristina

AU - Romieu, Isabelle

AU - Rookus, Matti A

AU - Rossing, Mary Anne

AU - Rzepecka, Iwona K

AU - Sandler, Dale P

AU - Schmutzler, Rita K

AU - Setiawan, Veronica W

AU - Sharma, Priyanka

AU - Sieh, Weiva

AU - Simard, Jacques

AU - Singer, Christian F

AU - Song, Honglin

AU - Southey, Melissa C

AU - Spurdle, Amanda B

AU - Sutphen, Rebecca

AU - Swerdlow, Anthony J

AU - Teixeira, Manuel R

AU - Teo, Soo H

AU - Thomassen, Mads

AU - Tischkowitz, Marc

AU - Toland, Amanda E

AU - Trichopoulou, Antonia

AU - Tung, Nadine

AU - Tworoger, Shelley S

AU - van Rensburg, Elizabeth J

AU - Vanderstichele, Adriaan

AU - Vega, Ana

AU - Edwards, Digna Velez

AU - Webb, Penelope M

AU - Weitzel, Jeffrey N

AU - Wentzensen, Nicolas

AU - White, Emily

AU - Wolk, Alicja

AU - Wu, Anna H

AU - Yannoukakos, Drakoulis

AU - Zorn, Kristin K

AU - Gayther, Simon A

AU - Antoniou, Antonis C

AU - Berchuck, Andrew

AU - Goode, Ellen L

AU - Chenevix-Trench, Georgia

AU - Sellers, Thomas A

AU - Pharoah, Paul D P

AU - Zheng, Wei

AU - Long, Jirong

PY - 2018/9/15

Y1 - 2018/9/15

N2 - Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their

AB - Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their

KW - Eggjastokkar

KW - Krabbamein

KW - Gen

KW - Ovarian Neoplasms

KW - Genome-Wide Association Study

KW - Eggjastokkar

KW - Krabbamein

KW - Gen

KW - Ovarian Neoplasms

KW - Genome-Wide Association Study

U2 - 10.1158/0008-5472.CAN-18-0951

DO - 10.1158/0008-5472.CAN-18-0951

M3 - Article

C2 - 30054336

SN - 1538-7445

JO - Cancer Research

JF - Cancer Research

ER -

A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Abstract

Other keywords

UN SDGs

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