The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk

A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk
A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk

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 cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 106, we identified 35 genes, including FZD4 at 11q14.2 (Z ¼ 5.08, P ¼ 3.83 107, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 103). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.

0008-5472
5419-5430
Lu, Yingchang
58bede2f-02f6-42c9-9eb1-cd1d030144aa
Beeghly-Fadiel, Alicia
d0355d79-a847-41fd-90b5-ddf0879f4b72
Wu, Lang
303d032b-124c-4c84-aa08-782bf819f85c
Guo, Xingyi
1c79a12f-4fcb-4dec-b6f8-4c6bc442e3f5
Li, Bingshan
978344e2-92a2-40d2-b43e-c8c1fa6dd7c2
Schildkraut, Joellen M.
d52d66b9-4a15-48fd-97df-1bdc0696ea1a
Im, Hae Kyung
368b6de4-948e-4340-838f-a3bffb59d559
Chen, Yian A.
b2943b6d-a49d-4457-befa-d6f1ffc2ac59
Permuth, Jennifer B.
c12d4955-3a93-40a5-b4e9-58c908e1610f
Reid, Brett M.
95bc0c04-c6e3-42e7-9cd3-1d28baceafea
Teer, Jamie K.
3a154cc0-fc82-4358-8d97-b2542129c75c
Moysich, Kirsten B.
ffae45be-b72e-41d7-996a-fb5274800133
Andrulis, Irene L.
bc0d05b1-2437-452a-b9df-0d31cfbe1435
Anton-Culver, Hoda
6d8396d5-8d76-4207-a8f1-5729d5f2d0de
Arun, Banu K.
e4488a97-c261-40a0-b316-d8d5c26ffe00
Bandera, Elisa V.
4e52d275-b041-4f5f-a6af-a596ba0fcde1
Barkardottir, Rosa B.
997ac890-d2ce-4fad-b556-d7f48003ae8e
Barnes, Daniel R.
92a2a7e0-5336-4353-a31a-126ad4fd3d4c
Benitez, Javier
aaf768e0-3166-4656-a787-89512ca1828c
Bjorge, Line
d413e011-3b30-4d17-81ee-07d19c1667fa
Brenton, James
834c3a0f-a453-4de5-908d-c5c21f1533af
Butzow, Ralf
77e849a3-7e63-423f-bc1a-7bf95b2028d1
Caldes, Trinidad
8caab9c0-bec3-44d5-8e98-c97ee3ebda7d
Caligo, Maria A.
8fd95b7b-5e69-4f7f-9513-50b3d5e86ef6
Campbell, Ian
bca3ab80-1205-4f90-9ab9-434363811a40
Chang-Claude, Jenny
cf472d49-8420-41ff-8a38-b0148f0a7cae
Claes, Kathleen B.M.
311e99c7-118f-4e50-a298-15ddd60d5a52
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Cramer, Daniel W.
9c40e027-08c3-4bf1-8c6e-39de9f11a620
Daly, Mary B.
7d327e18-8795-40e7-af04-5dad9a3f82aa
DeFazio, Anna
3a9c3643-0572-4a28-a233-600ad5867d74
Dennis, Joe
bd305c84-d968-4946-b154-a5bedb469210
Diez, Orland
35522b1a-2862-43ce-b8e9-50f60579c671
Domchek, Susan M.
7d99c293-81c9-4f0e-ab2c-e2655e2b601e
D rk, Thilo
103e5b2e-17e4-4c33-8b94-ce9d3979d709
Easton, Douglas F.
386c61f7-8b57-49d9-a0cc-addb10360598
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Fasching, Peter A.
28905b56-c431-479b-8687-98d5858e04e9
Fortner, Ren e.T.
b6320e5b-284a-411e-b829-1378dc8c5438
Fountzilas, George
c459d95d-1116-4828-a56c-5c638129a9ae
Friedman, Eitan
764d4102-31ee-4826-ad68-0da74dba88f2
Ganz, Patricia A.
e7573e53-13b2-4291-80d8-a59249b827fe
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Giles, Graham G.
e0cc73eb-c8eb-450b-b566-fc05e0d2dee3
Godwin, Andrew K.
a7e89dce-59e1-48f7-b668-42777f362435
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Goodman, Marc T.
fc194370-ee36-4bdf-91af-13a5a9cc0cfa
Greene, Mark H.
aefbcd26-0def-47a3-8580-0c56feb03756
Gronwald, Jacek
4a0117ac-84f8-4351-a97d-637a60db25f6
Hamann, Ute
c47a5052-5e7b-492c-988b-38b7df2cffc6
Heitz, Florian
18b5c90e-015e-4444-9069-5a1f4cdc223c
Hildebrandt, Michelle A.T.
6f596824-8f45-40d1-922d-889cc938a5f5
Høgdall, Claus K.
b44e3a82-88dd-4f7d-84c8-07f45eec2702
Hollestelle, Antoinette
9a0046d0-fb69-4346-be76-fcb6858ff33f
Hulick, Peter J.
8e5971bf-5f9f-404f-baa6-b61f47cb13ce
Huntsman, David G.
c6c80374-9f3f-41d4-8363-288660bf7cc8
Imyanitov, Evgeny N.
fcad02c1-95af-47aa-9b1b-3ea64cd20d99
Isaacs, Claudine
6e60951b-1f07-471a-8ca3-1941e83bbf83
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
James, Paul
ca41caad-4a55-4fe4-9b7a-0b2b4d9a5917
Karlan, Beth Y.
0a74d552-f43d-4670-bc0c-0f860d55b15e
Kelemen, Linda E.
20d9f9ac-ec73-4832-8f28-61257497af0b
Kiemeney, Lambertus A.
a6af871e-f8d5-4a1f-a114-842b0f2a88e2
Kjaer, Susanne K.
cbc4dca5-85cf-4f57-a19d-3e47af44e8fc
Kwong, Ava
0e3a4ee7-f400-4da7-8a3c-9183eb75ac66
Le, Nhu D.
a1cf60be-f2a2-409c-bd22-4a3e0b22e847
Leslie, Goska
e07ce1c8-bf6f-466b-a1d7-48759af37252
Lesueur, Fabienne
13602e4a-bb59-463b-a272-0dcbc7e25b22
Levine, Douglas A.
ddb85640-ee51-41bf-98d5-13fcb3f13e09
Mattiello, Amalia
abe9476f-de3a-4b28-a580-cbde3d749964
May, Taymaa
928bd830-83b8-4489-a59c-e9fc38a74af8
McGuffog, Lesley
21522096-38bb-45df-aa56-caf2f27d7254
McNeish, Iain A.
3d4abc4b-4b74-45ed-8c71-80dcc7bc2ee8
Merritt, Melissa A.
75c7cfd4-dd1e-4729-ae05-456d4e089cc4
Modugno, Francesmary
a234d152-a897-42f8-8ea5-c04081310c3b
Montagna, Marco
1e04949f-87c3-4ca4-a772-5d59a9407f07
Neuhausen, Susan L.
7cb359d3-5964-460c-ad60-63b77368c042
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Nielsen, Finn C.
38defc00-22e2-4d73-9ad3-18a4115d926c
Nikitina-Zake, Liene
c184db10-5db8-4e91-9aab-b4cbc4475a61
Nussbaum, Robert L.
050ecb33-a74c-4553-8e33-793931e86b13
Offit, Kenneth
ce1fc8a6-b5ac-434a-9d2d-4a7e1ee7ca7c
Olah, Edith
f4ee7e40-b263-490e-96fc-84b98eb2ec20
Olopade, Olufunmilayo I.
c926d080-7dfd-49f7-ab2f-95a8e24365cc
Olson, Sara H.
90516ad2-df99-492f-9aa1-52c2f135d444
Olsson, H. kan
4b5dd481-e6b9-4dc0-926f-e4184a37a914
Osorio, Ana
5d37d9d7-d889-4e14-ad7c-7b7f73f6e299
Park, Sue K.
d49e7c29-0a06-4a44-8230-7920ec31a934
Parsons, Michael T.
b573d8d3-85a2-4232-808e-200e60865953
Peeters, Petra H.M.
891cacd8-457f-423d-ac6b-69c7a4f8b5c8
Pejovic, Tanja
74afdf27-a8d3-4f63-877e-053cbac1d3d4
Peterlongo, Paolo
af3f3db4-e3fc-45db-bbb4-91954fe857fb
Phelan, Catherine M.
0692189d-5402-41da-a627-acc6ba0c6505
Pujana, Miquel Angel
b0b24c36-a004-449c-a1c6-ee75d82b08bf
Ramus, Susan J.
f2a91d0b-8aab-4e57-b49f-7637767b4f57
Rennert, Gad
76f7951d-133b-4b7e-86a2-175be20d775d
Risch, Harvey
ffea3438-29d4-4cea-b784-11438a0428cf
Rodriguez, Gustavo C.
2153f170-ed0f-43a3-8170-d9d97035f266
Rodríguez-Antona, Cristina
58160312-66eb-4cf6-a0f6-c49e2a963d72
Romieu, Isabelle
26369587-98ff-4280-abb5-140e7d462116
Rookus, Matti A.
9773a738-9a67-460f-9305-ecf35893eda2
Rossing, Mary Anne
a0f46209-683c-41c6-a7ba-366c7985775e
Rzepecka, Iwona K.
9cba996d-4e8e-4f1b-9117-3130aa6c445e
Sandler, Dale P.
24d170de-ad5a-4f8a-a312-069a4a24f235
Schmutzler, Rita K.
bf790f2e-79f3-4151-a74c-793bf14d8f6a
Setiawan, Veronica W.
57910336-5d91-4812-bf33-fbb888c9ff53
Sharma, Priyanka
aa5b0a3c-9f30-4933-b57f-1d100f20f55a
Sieh, Weiva
9d5bdd00-daee-4ad2-a93c-cabf9010a00d
Simard, Jacques
6269fd00-31ae-40f0-b016-5f60cb9f5b96
Singer, Christian F.
75cbba26-8c81-40be-9862-ef6d2392d5b0
Song, Honglin
90088f14-dc56-4280-83e3-71ad1744858d
Southey, Melissa C.
56062dff-748c-47e4-99f5-044cff9da594
Spurdle, Amanda B.
8158d468-cc96-4e39-9bac-fcaaa7061a72
Sutphen, Rebecca
67234e96-6ed8-4535-9abe-2ed7b8a73da9
Swerdlow, Anthony J.
5f6c764b-1374-49d1-bcee-1bdae5f47b9d
Teixeira, Manuel R.
bc0e9fc9-4f2f-4c30-a6ca-9c3a5e40a3bc
Teo, Soo H.
f48023c5-9e80-487b-83c7-f09563a9579d
Thomassen, Mads
c7c9230a-4f3d-42d0-89f1-b5a36d431aae
Tischkowitz, Marc
3c5f5429-fb53-4c80-8a42-6cec37ab67bc
Toland, Amanda E.
f9fbf6de-815a-4dd6-a576-2376273be8bd
Trichopoulou, Antonia
57c66700-6977-4218-b8f3-e9064f93a873
Tung, Nadine
9a999423-a6aa-41a5-957f-2d788ee3da15
Tworoger, Shelley S.
7016b048-06b3-43dd-a660-2bf19b34c3c1
Van Rensburg, Elizabeth J.
d4dd3b97-d9ee-4968-97f4-4e8aa97c574a
Vanderstichele, Adriaan
b612a688-4241-44d9-8cae-d6e3638ac66a
Vega, Ana
fad461f9-0796-4a2b-927b-cb0fc83478cd
Edwards, Digna Velez
972cd86b-c51d-437a-8a8a-dba8755564aa
Webb, Penelope M.
5b700002-183d-4eea-87f9-71b77fe6f41d
Weitzel, Jeffrey N.
f3a4bc20-189c-4655-af63-d8b8e3ea6055
Wentzensen, Nicolas
43ddba47-f169-466d-b6aa-c2f5a20e9753
White, Emily
5f99bc6d-4c8c-46fd-9bda-53e4d205710b
Wolk, Alicja
b49ba21f-ee91-4459-b309-38dbf2daefb3
Wu, Anna H.
a657c0a4-2887-4b9c-a018-a795197920e3
Yannoukakos, Drakoulis
b3f8728f-9538-4b45-84b1-dfe08bb0d3b8
Zorn, Kristin K.
15fa3872-71b5-473f-b7a1-906661a31bf3
Gayther, Simon A.
5333cc14-fc1e-4517-9808-be39b0fb009c
Antoniou, Antonis C.
e5c475a7-25bb-4973-b7aa-689c00c7edab
Berchuck, Andrew
1e234fbd-4421-49d8-9fbf-b19098d71434
Goode, Ellen L.
e57c9220-6e9e-42d4-bc4c-6f4571505a64
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Sellers, Thomas A.
af3ae8a7-365a-4b5c-a057-474380f575ab
Pharoah, Paul D.P.
ca299de1-a3c4-4812-bc2f-00d1c3684e99
Zheng, Wei
e8338ae7-b60e-46dd-bf1b-7648891c6fe4
Long, Jirong
67a02641-1b7d-4019-938d-c2b27a5c7ae8
Lu, Yingchang
58bede2f-02f6-42c9-9eb1-cd1d030144aa
Beeghly-Fadiel, Alicia
d0355d79-a847-41fd-90b5-ddf0879f4b72
Wu, Lang
303d032b-124c-4c84-aa08-782bf819f85c
Guo, Xingyi
1c79a12f-4fcb-4dec-b6f8-4c6bc442e3f5
Li, Bingshan
978344e2-92a2-40d2-b43e-c8c1fa6dd7c2
Schildkraut, Joellen M.
d52d66b9-4a15-48fd-97df-1bdc0696ea1a
Im, Hae Kyung
368b6de4-948e-4340-838f-a3bffb59d559
Chen, Yian A.
b2943b6d-a49d-4457-befa-d6f1ffc2ac59
Permuth, Jennifer B.
c12d4955-3a93-40a5-b4e9-58c908e1610f
Reid, Brett M.
95bc0c04-c6e3-42e7-9cd3-1d28baceafea
Teer, Jamie K.
3a154cc0-fc82-4358-8d97-b2542129c75c
Moysich, Kirsten B.
ffae45be-b72e-41d7-996a-fb5274800133
Andrulis, Irene L.
bc0d05b1-2437-452a-b9df-0d31cfbe1435
Anton-Culver, Hoda
6d8396d5-8d76-4207-a8f1-5729d5f2d0de
Arun, Banu K.
e4488a97-c261-40a0-b316-d8d5c26ffe00
Bandera, Elisa V.
4e52d275-b041-4f5f-a6af-a596ba0fcde1
Barkardottir, Rosa B.
997ac890-d2ce-4fad-b556-d7f48003ae8e
Barnes, Daniel R.
92a2a7e0-5336-4353-a31a-126ad4fd3d4c
Benitez, Javier
aaf768e0-3166-4656-a787-89512ca1828c
Bjorge, Line
d413e011-3b30-4d17-81ee-07d19c1667fa
Brenton, James
834c3a0f-a453-4de5-908d-c5c21f1533af
Butzow, Ralf
77e849a3-7e63-423f-bc1a-7bf95b2028d1
Caldes, Trinidad
8caab9c0-bec3-44d5-8e98-c97ee3ebda7d
Caligo, Maria A.
8fd95b7b-5e69-4f7f-9513-50b3d5e86ef6
Campbell, Ian
bca3ab80-1205-4f90-9ab9-434363811a40
Chang-Claude, Jenny
cf472d49-8420-41ff-8a38-b0148f0a7cae
Claes, Kathleen B.M.
311e99c7-118f-4e50-a298-15ddd60d5a52
Couch, Fergus J.
778e32f1-0b19-4cf4-b38f-69dd027cad3a
Cramer, Daniel W.
9c40e027-08c3-4bf1-8c6e-39de9f11a620
Daly, Mary B.
7d327e18-8795-40e7-af04-5dad9a3f82aa
DeFazio, Anna
3a9c3643-0572-4a28-a233-600ad5867d74
Dennis, Joe
bd305c84-d968-4946-b154-a5bedb469210
Diez, Orland
35522b1a-2862-43ce-b8e9-50f60579c671
Domchek, Susan M.
7d99c293-81c9-4f0e-ab2c-e2655e2b601e
D rk, Thilo
103e5b2e-17e4-4c33-8b94-ce9d3979d709
Easton, Douglas F.
386c61f7-8b57-49d9-a0cc-addb10360598
Eccles, Diana M.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Fasching, Peter A.
28905b56-c431-479b-8687-98d5858e04e9
Fortner, Ren e.T.
b6320e5b-284a-411e-b829-1378dc8c5438
Fountzilas, George
c459d95d-1116-4828-a56c-5c638129a9ae
Friedman, Eitan
764d4102-31ee-4826-ad68-0da74dba88f2
Ganz, Patricia A.
e7573e53-13b2-4291-80d8-a59249b827fe
Garber, Judy
fdc6e441-ff06-4864-a716-75cb3a8a93de
Giles, Graham G.
e0cc73eb-c8eb-450b-b566-fc05e0d2dee3
Godwin, Andrew K.
a7e89dce-59e1-48f7-b668-42777f362435
Goldgar, David E.
102af7b6-41ab-46c0-9d76-43359c897e2e
Goodman, Marc T.
fc194370-ee36-4bdf-91af-13a5a9cc0cfa
Greene, Mark H.
aefbcd26-0def-47a3-8580-0c56feb03756
Gronwald, Jacek
4a0117ac-84f8-4351-a97d-637a60db25f6
Hamann, Ute
c47a5052-5e7b-492c-988b-38b7df2cffc6
Heitz, Florian
18b5c90e-015e-4444-9069-5a1f4cdc223c
Hildebrandt, Michelle A.T.
6f596824-8f45-40d1-922d-889cc938a5f5
Høgdall, Claus K.
b44e3a82-88dd-4f7d-84c8-07f45eec2702
Hollestelle, Antoinette
9a0046d0-fb69-4346-be76-fcb6858ff33f
Hulick, Peter J.
8e5971bf-5f9f-404f-baa6-b61f47cb13ce
Huntsman, David G.
c6c80374-9f3f-41d4-8363-288660bf7cc8
Imyanitov, Evgeny N.
fcad02c1-95af-47aa-9b1b-3ea64cd20d99
Isaacs, Claudine
6e60951b-1f07-471a-8ca3-1941e83bbf83
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
James, Paul
ca41caad-4a55-4fe4-9b7a-0b2b4d9a5917
Karlan, Beth Y.
0a74d552-f43d-4670-bc0c-0f860d55b15e
Kelemen, Linda E.
20d9f9ac-ec73-4832-8f28-61257497af0b
Kiemeney, Lambertus A.
a6af871e-f8d5-4a1f-a114-842b0f2a88e2
Kjaer, Susanne K.
cbc4dca5-85cf-4f57-a19d-3e47af44e8fc
Kwong, Ava
0e3a4ee7-f400-4da7-8a3c-9183eb75ac66
Le, Nhu D.
a1cf60be-f2a2-409c-bd22-4a3e0b22e847
Leslie, Goska
e07ce1c8-bf6f-466b-a1d7-48759af37252
Lesueur, Fabienne
13602e4a-bb59-463b-a272-0dcbc7e25b22
Levine, Douglas A.
ddb85640-ee51-41bf-98d5-13fcb3f13e09
Mattiello, Amalia
abe9476f-de3a-4b28-a580-cbde3d749964
May, Taymaa
928bd830-83b8-4489-a59c-e9fc38a74af8
McGuffog, Lesley
21522096-38bb-45df-aa56-caf2f27d7254
McNeish, Iain A.
3d4abc4b-4b74-45ed-8c71-80dcc7bc2ee8
Merritt, Melissa A.
75c7cfd4-dd1e-4729-ae05-456d4e089cc4
Modugno, Francesmary
a234d152-a897-42f8-8ea5-c04081310c3b
Montagna, Marco
1e04949f-87c3-4ca4-a772-5d59a9407f07
Neuhausen, Susan L.
7cb359d3-5964-460c-ad60-63b77368c042
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Nielsen, Finn C.
38defc00-22e2-4d73-9ad3-18a4115d926c
Nikitina-Zake, Liene
c184db10-5db8-4e91-9aab-b4cbc4475a61
Nussbaum, Robert L.
050ecb33-a74c-4553-8e33-793931e86b13
Offit, Kenneth
ce1fc8a6-b5ac-434a-9d2d-4a7e1ee7ca7c
Olah, Edith
f4ee7e40-b263-490e-96fc-84b98eb2ec20
Olopade, Olufunmilayo I.
c926d080-7dfd-49f7-ab2f-95a8e24365cc
Olson, Sara H.
90516ad2-df99-492f-9aa1-52c2f135d444
Olsson, H. kan
4b5dd481-e6b9-4dc0-926f-e4184a37a914
Osorio, Ana
5d37d9d7-d889-4e14-ad7c-7b7f73f6e299
Park, Sue K.
d49e7c29-0a06-4a44-8230-7920ec31a934
Parsons, Michael T.
b573d8d3-85a2-4232-808e-200e60865953
Peeters, Petra H.M.
891cacd8-457f-423d-ac6b-69c7a4f8b5c8
Pejovic, Tanja
74afdf27-a8d3-4f63-877e-053cbac1d3d4
Peterlongo, Paolo
af3f3db4-e3fc-45db-bbb4-91954fe857fb
Phelan, Catherine M.
0692189d-5402-41da-a627-acc6ba0c6505
Pujana, Miquel Angel
b0b24c36-a004-449c-a1c6-ee75d82b08bf
Ramus, Susan J.
f2a91d0b-8aab-4e57-b49f-7637767b4f57
Rennert, Gad
76f7951d-133b-4b7e-86a2-175be20d775d
Risch, Harvey
ffea3438-29d4-4cea-b784-11438a0428cf
Rodriguez, Gustavo C.
2153f170-ed0f-43a3-8170-d9d97035f266
Rodríguez-Antona, Cristina
58160312-66eb-4cf6-a0f6-c49e2a963d72
Romieu, Isabelle
26369587-98ff-4280-abb5-140e7d462116
Rookus, Matti A.
9773a738-9a67-460f-9305-ecf35893eda2
Rossing, Mary Anne
a0f46209-683c-41c6-a7ba-366c7985775e
Rzepecka, Iwona K.
9cba996d-4e8e-4f1b-9117-3130aa6c445e
Sandler, Dale P.
24d170de-ad5a-4f8a-a312-069a4a24f235
Schmutzler, Rita K.
bf790f2e-79f3-4151-a74c-793bf14d8f6a
Setiawan, Veronica W.
57910336-5d91-4812-bf33-fbb888c9ff53
Sharma, Priyanka
aa5b0a3c-9f30-4933-b57f-1d100f20f55a
Sieh, Weiva
9d5bdd00-daee-4ad2-a93c-cabf9010a00d
Simard, Jacques
6269fd00-31ae-40f0-b016-5f60cb9f5b96
Singer, Christian F.
75cbba26-8c81-40be-9862-ef6d2392d5b0
Song, Honglin
90088f14-dc56-4280-83e3-71ad1744858d
Southey, Melissa C.
56062dff-748c-47e4-99f5-044cff9da594
Spurdle, Amanda B.
8158d468-cc96-4e39-9bac-fcaaa7061a72
Sutphen, Rebecca
67234e96-6ed8-4535-9abe-2ed7b8a73da9
Swerdlow, Anthony J.
5f6c764b-1374-49d1-bcee-1bdae5f47b9d
Teixeira, Manuel R.
bc0e9fc9-4f2f-4c30-a6ca-9c3a5e40a3bc
Teo, Soo H.
f48023c5-9e80-487b-83c7-f09563a9579d
Thomassen, Mads
c7c9230a-4f3d-42d0-89f1-b5a36d431aae
Tischkowitz, Marc
3c5f5429-fb53-4c80-8a42-6cec37ab67bc
Toland, Amanda E.
f9fbf6de-815a-4dd6-a576-2376273be8bd
Trichopoulou, Antonia
57c66700-6977-4218-b8f3-e9064f93a873
Tung, Nadine
9a999423-a6aa-41a5-957f-2d788ee3da15
Tworoger, Shelley S.
7016b048-06b3-43dd-a660-2bf19b34c3c1
Van Rensburg, Elizabeth J.
d4dd3b97-d9ee-4968-97f4-4e8aa97c574a
Vanderstichele, Adriaan
b612a688-4241-44d9-8cae-d6e3638ac66a
Vega, Ana
fad461f9-0796-4a2b-927b-cb0fc83478cd
Edwards, Digna Velez
972cd86b-c51d-437a-8a8a-dba8755564aa
Webb, Penelope M.
5b700002-183d-4eea-87f9-71b77fe6f41d
Weitzel, Jeffrey N.
f3a4bc20-189c-4655-af63-d8b8e3ea6055
Wentzensen, Nicolas
43ddba47-f169-466d-b6aa-c2f5a20e9753
White, Emily
5f99bc6d-4c8c-46fd-9bda-53e4d205710b
Wolk, Alicja
b49ba21f-ee91-4459-b309-38dbf2daefb3
Wu, Anna H.
a657c0a4-2887-4b9c-a018-a795197920e3
Yannoukakos, Drakoulis
b3f8728f-9538-4b45-84b1-dfe08bb0d3b8
Zorn, Kristin K.
15fa3872-71b5-473f-b7a1-906661a31bf3
Gayther, Simon A.
5333cc14-fc1e-4517-9808-be39b0fb009c
Antoniou, Antonis C.
e5c475a7-25bb-4973-b7aa-689c00c7edab
Berchuck, Andrew
1e234fbd-4421-49d8-9fbf-b19098d71434
Goode, Ellen L.
e57c9220-6e9e-42d4-bc4c-6f4571505a64
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Sellers, Thomas A.
af3ae8a7-365a-4b5c-a057-474380f575ab
Pharoah, Paul D.P.
ca299de1-a3c4-4812-bc2f-00d1c3684e99
Zheng, Wei
e8338ae7-b60e-46dd-bf1b-7648891c6fe4
Long, Jirong
67a02641-1b7d-4019-938d-c2b27a5c7ae8

Lu, Yingchang, Beeghly-Fadiel, Alicia, Wu, Lang, Guo, Xingyi, Li, Bingshan, Schildkraut, Joellen M., Im, Hae Kyung, Chen, Yian A., Permuth, Jennifer B., Reid, Brett M., Teer, Jamie K., Moysich, Kirsten B., Andrulis, Irene L., Anton-Culver, Hoda, Arun, Banu K., Bandera, Elisa V., Barkardottir, Rosa B., Barnes, Daniel R., Benitez, Javier, Bjorge, Line, Brenton, James, Butzow, Ralf, Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Chang-Claude, Jenny, Claes, Kathleen B.M., Couch, Fergus J., Cramer, Daniel W., Daly, Mary B., DeFazio, Anna, Dennis, Joe, Diez, Orland, Domchek, Susan M., D rk, Thilo, Easton, Douglas F., Eccles, Diana M., Fasching, Peter A., Fortner, Ren e.T., Fountzilas, George, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Giles, Graham G., Godwin, Andrew K., Goldgar, David E., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Hamann, Ute, Heitz, Florian, Hildebrandt, Michelle A.T., Høgdall, Claus K., Hollestelle, Antoinette, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul, Karlan, Beth Y., Kelemen, Linda E., Kiemeney, Lambertus A., Kjaer, Susanne K., Kwong, Ava, Le, Nhu D., Leslie, Goska, Lesueur, Fabienne, Levine, Douglas A., Mattiello, Amalia, May, Taymaa, McGuffog, Lesley, McNeish, Iain A., Merritt, Melissa A., Modugno, Francesmary, Montagna, Marco, Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., Nikitina-Zake, Liene, Nussbaum, Robert L., Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Sara H., Olsson, H. kan, Osorio, Ana, Park, Sue K., Parsons, Michael T., Peeters, Petra H.M., Pejovic, Tanja, Peterlongo, Paolo, Phelan, Catherine M., Pujana, Miquel Angel, Ramus, Susan J., Rennert, Gad, Risch, Harvey, Rodriguez, Gustavo C., Rodríguez-Antona, Cristina, Romieu, Isabelle, Rookus, Matti A., Rossing, Mary Anne, Rzepecka, Iwona K., Sandler, Dale P., Schmutzler, Rita K., Setiawan, Veronica W., Sharma, Priyanka, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Song, Honglin, Southey, Melissa C., Spurdle, Amanda B., Sutphen, Rebecca, Swerdlow, Anthony J., Teixeira, Manuel R., Teo, Soo H., Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E., Trichopoulou, Antonia, Tung, Nadine, Tworoger, Shelley S., Van Rensburg, Elizabeth J., Vanderstichele, Adriaan, Vega, Ana, Edwards, Digna Velez, Webb, Penelope M., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Wolk, Alicja, Wu, Anna H., Yannoukakos, Drakoulis, Zorn, Kristin K., Gayther, Simon A., Antoniou, Antonis C., Berchuck, Andrew, Goode, Ellen L., Chenevix-Trench, Georgia, Sellers, Thomas A., Pharoah, Paul D.P., Zheng, Wei and Long, Jirong (2018) A transcriptome-wide association study among 97,898 women to identify candidate susceptibility genes for epithelial ovarian cancer risk. Cancer Research, 78 (18), 5419-5430. (doi:10.1158/0008-5472.CAN-18-0951).

Record type: Article

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 cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 106, we identified 35 genes, including FZD4 at 11q14.2 (Z ¼ 5.08, P ¼ 3.83 107, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 103). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.

This record has no associated files available for download.

More information

Accepted/In Press date: 24 July 2018
e-pub ahead of print date: 27 July 2018
Published date: 15 September 2018

Identifiers

Local EPrints ID: 425775
URI: http://eprints.soton.ac.uk/id/eprint/425775
ISSN: 0008-5472
PURE UUID: d1e0ef69-b02c-4488-9569-048df7df9495
ORCID for Diana M. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 02 Nov 2018 17:30
Last modified: 26 Nov 2021 02:34

Export record

Altmetrics

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×