The University of Southampton
University of Southampton Institutional Repository

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
genome-wide association studies, genomics, neurodegenerative diseases
1061-4036
134-143
Fritsche, Lars G.
5f2b0f97-1994-4658-baf5-c74dcdab3a2e
Igl, Wilmar
a3722cdf-0a15-4b60-a069-407c5edb52be
Cooke Bailey, Jessica N.
192ad3eb-5f5e-4817-a50d-9ca4ce9720c1
Grassmann, Felix
a72edc86-c7e0-495f-a827-51d7db514076
Sengupta, Sebanti
e095ad27-7e6d-447a-a04d-70297e5ad4a0
Bragg-Gresham, Jennifer L.
70aa0364-24d9-4527-8027-c6f6053d90ce
Burdon, Kathryn P.
34420e05-5749-451e-827c-38e3f36d2f58
Hebbring, Scott J.
beeb0ecf-27c2-4c86-b914-c1aa133fd1c4
Wen, Cindy
1a23ac3a-87f6-492b-8ba1-6f9c3bbb2f04
Gorski, Mathias
b75bf9b7-7456-47cb-93de-1611569e843b
Kim, Ivana K.
555c047a-270b-41ff-9514-0f1c9aed0573
Cho, David
0e28ef93-9b86-4f72-ab9c-1b146f72035d
Zack, Donald
d8106848-2f0f-490f-9339-5ea6716503ae
Souied, Eric
f99aa288-924d-43c9-9f82-6d2eb3f4f6a8
Scholl, Hendrik P.N.
2c38ca3c-90a8-455d-a22c-b52508a9890e
Bala, Elisa
353206a4-c3eb-4e56-93cd-ab7e20d1366e
Lee, Kristine E.
68503d7b-a431-4f51-9bf1-59f2c3bdf5aa
Hunter, David J.
2a7b7bbf-a9cc-4a70-8d2a-fbb169501a14
Sardell, Rebecca J.
a91abc89-3e13-4258-adf4-9944d55cf408
Mitchell, Paul
b2bb46ab-6cd6-44fa-9b4a-b96a50650236
Merriam, Joanna E.
66fe67e6-82a5-4840-b1ef-ea38c3ea92a8
Cipriani, Valentina
df4a538c-6639-45c5-818a-255aa59b44cf
Hoffman, Joshua D.
0081f5ac-e49f-46c5-8b2f-7d45a7ecbc48
Schick, Tina
e42452ef-7716-4037-a135-40b221e447e9
Lechanteur, Yara T.E.
7d0c7c26-818d-4074-b0bd-e0f321f25e6c
Guymer, Robyn H.
ce21dd40-50d0-439a-bb21-b8ad044a721c
Johnson, Matthew P.
6318d310-f146-459e-aa87-a43a1ef7dbc3
Jiang, Yingda
a7ded535-28f3-490e-9889-968a753f32b2
Stanton, Chloe M.
e49a140e-86a0-46f4-a109-fde65288d457
Buitendijk, Gabriëlle H.S.
b7db3a9c-4ec0-487d-a758-221178c60da3
Zhan, Xiaowei
4cf61199-f167-44cf-bc22-3971ee962287
Kwong, Alan M.
d604b200-77eb-431b-bb89-7fe7aaf4ab35
Boleda, Alexis
848ad413-3d6e-45b5-bc32-4b4c535723de
Brooks, Matthew
50228f36-2eda-41f6-b27e-4acbaf8a0a6f
Gieser, Linn
a95498e7-982d-43bc-a83a-e2126a436078
Ratnapriya, Rinki
32da91bd-89f5-4c79-89d9-ff60a3140c96
Branham, Kari E.
c9863a7b-eb01-4523-818e-81752386efd8
Foerster, Johanna R.
7f344fbc-d01e-41d5-b7d4-29cc8306a524
Heckenlively, John R.
c048f769-0ec9-4275-bc54-8cc2a6ec6b05
Othman, Mohammad I.
4e6e5486-b4c3-43b8-a217-96e7456aee7f
Vote, Brendan J.
0a0d04ba-73de-49b9-a244-f959b310a6dc
Liang, Helena Hai
f6b33d3a-73cc-491a-86bb-41fe68353a38
Souzeau, Emmanuelle
005c82f2-d220-4995-b722-bab94749eb9b
McAllister, Ian L.
2a7f95af-8fa8-4c9e-9f51-1729d1d84dce
Isaacs, Timothy
5058b914-d851-446a-a52f-3619f74ba5b0
Hall, Janette
71442469-e771-43f4-a31d-5b05a9247b3d
Lake, Stewart
13e2177f-fb3c-4091-955e-b2c6d7c3162a
Mackey, David A.
b627e9fd-68dd-4473-bfb4-c05d98cdd941
Constable, Ian J.
22679d65-bc32-43ed-bf98-a824fd7b262f
Craig, Jamie E.
795b9c1d-b781-4a27-90ce-cd0ddaa70a9a
Kitchner, Terrie E.
2cbd80e1-1325-4022-9e81-c2ffc97d7c56
Yang, Zhenglin
15c73a06-6c68-4519-b997-7947feb8d588
Su, Zhiguang
392ee7e4-18dd-4aa3-acbd-a2b742eaba45
Luo, Hongrong
41f5d9a3-c480-4ca5-9bf8-ed767df6550b
Chen, Daniel
968712bc-546b-45f9-96f4-4d3627336b38
Ouyang, Hong
80b6393b-e171-4e64-8eb9-89c912321f29
Flagg, Ken
74545534-2bb2-418b-b418-c623fb0c444d
Lin, Danni
ef95c2bf-7bd7-450e-a944-7a8380f32a6d
Mao, Guanping
4477be3d-e529-4145-808f-adf5a917219f
Ferreyra, Henry
5ba787f6-9bfe-4d32-bf63-423e3a3ddcf0
Stark, Klaus
a16b88de-ef50-4cbc-a104-75e0befeae4e
von Strachwitz, Claudia N.
d9087fa4-2455-4c40-a882-87be6fbecb77
Wolf, Armin
bc61d48f-3535-4f40-8a7d-7a13650fe7a3
Brandl, Caroline
4b539276-dcd9-4041-a762-6080a3ae42d9
Rudolph, Guenther
8e26f35f-4331-4bea-97b8-98b008dc42c1
Olden, Matthias
48408f0b-936a-44d3-b7e5-213d5eb60269
Morrison, Margaux A.
6e5f7330-cb0c-466e-9449-fed4374fd3d7
Morgan, Denise J
c6947006-86e4-4ef3-a726-2dc07a20ee03
Schu, Matthew
53413e5b-742f-4b93-86e3-e6862022b371
Ahn, Jeeyun
6de22257-f696-476b-a97f-224f4adbb8e7
Silvestri, Giuliana
8552d5e4-db6e-41b4-857f-967dffcd8712
Tsironi, Evangelia E.
c61bf54a-bcef-4c67-876a-16f7d27def5b
Park, Kyu Hyung
d88b3f1c-81b9-4646-b517-425a717d87e0
Farrer, Lindsay A.
5e0f83bf-3eb9-458a-b750-f1e608499e48
Orlin, Anton
855323dc-11b5-4a11-83b2-b9d0d57a5834
Brucker, Alexander
f59dcc34-3a0f-4cdd-bedb-635e3d9f7b61
Li, Mingyao
81e6fd8b-50cb-4939-8530-f87be479b58c
Curcio, Christine A.
0467a2bc-35aa-471d-864a-f845ffec1ed5
Mohand-Saïd, Saddek
885b25d3-51cc-428e-add2-443e8d712c9a
Sahel, José-Alain
4f3dfd82-08f2-4fac-b46f-43d7c7501857
Audo, Isabelle
6941f4f3-9139-4d9c-ba6c-371fe7eec722
Benchaboune, Mustapha
32094a93-5a9f-4c13-b0e4-806da3cbbdaf
Cree, Angela J.
6724b71b-8828-4abb-971f-0856c2af555e
Rennie, Christina A.
774e5501-a414-47b8-a036-ee3adb226fc2
Goverdhan, Srinivas V.
9ae32d5a-5c82-48a4-962d-1ed8acc3991e
Grunin, Michelle
4a3152f1-9fc1-41ef-ad3f-fb7da4655bbc
Hagbi-Levi, Shira
2c5bfd04-e2a9-492b-ba5b-d58f853c7fbe
Campochiaro, Peter
fdc7fdfe-dba3-4b19-a9bf-fb02659a60cf
Katsanis, Nicholas
84c1ae0d-8198-41c6-91da-07330b39dd0d
Holz, Frank G.
c31bba20-ea0a-4937-ba14-22395fa08f66
Blond, Frédéric
49520eb6-264a-496f-b4ba-b98c7d14235a
Blanché, Hélène
dfa6ea8e-1b32-40c2-8c61-855a685dcc2c
Deleuze, Jean-François
92fd4dc3-0244-4167-8f15-540ad7e1d63d
Igo, Robert P.
c88ecc47-78a4-4b03-980c-542c56cb38b7
Truitt, Barbara
eae91ef1-fe6a-4220-a1a3-cd543a42262f
Peachey, Neal S.
42099a42-cf34-49f9-a686-b481bdedd5a8
Meuer, Stacy M.
77532ffa-a078-43ce-9384-ce64578e48e0
Myers, Chelsea E.
9cdea256-c976-4799-a17d-ca71c3717636
Moore, Emily L.
ef3d0979-8a88-467a-ac67-8d3c05a271c0
Klein, Ronald
3cce2b44-6cd3-4a91-bf9e-bfb9d5764dde
Hauser, Michael A.
7770a8b2-8c45-4d4e-9435-5c239d8b4258
Postel, Eric A.
1b24eb1e-1324-4f88-aa7c-3d3a5b0628d1
Courtenay, Monique D.
eb7de201-5a93-4eb7-89ab-7e6f41433329
Schwartz, Stephen G.
3f642455-f396-4a43-a3e1-6bc67369b942
Kovach, Jaclyn L.
5f781211-a06f-48fe-bbce-adfabd8a522a
Scott, William K.
a59d2b10-185f-4660-a9f4-4af0774bea09
Liew, Gerald
31018dd0-8742-4454-8c5b-70e25580fa15
Tan, Ava G.
92d59a47-43d8-490d-96e2-51b1db1eacfa
Gopinath, Bamini
e5044b3d-92c9-4dc9-bd31-8e527149b2e9
Merriam, John C.
19704ca6-c497-48be-915a-6efbb67b3cb1
Smith, R. Theodore
58d37a6a-a5c0-4906-b60a-6826457ab3fc
Khan, Jane C.
6f6d25de-f390-4cdb-8b3c-ce5e5bce5d9d
Shahid, Humma
f5e43d4f-13e1-4779-af60-f41a93ed6891
Moore, Anthony T.
b354a26a-bed7-4a54-a3ab-32083c425f33
McGrath, J. Allie
d18310bc-3284-4178-83e7-ca553609cc91
Laux, Reneé
c048f4ba-e9b2-4b8f-adc6-4a45b8c80853
Brantley, Milam A.
224a5868-7e26-4319-97f7-242dbaba5c71
Agarwal, Anita
8970b628-caf0-4f2b-b83c-ca29ca9ba2b3
Ersoy, Lebriz
e132d24e-9cad-4681-8e0f-6d33fbbb10dc
Caramoy, Albert
d78d8730-6196-4de8-a0dd-92080860ec30
Langmann, Thomas
0c511bfb-a720-40c3-8d19-ca964ed991cb
Saksens, Nicole T.M.
c69bf85d-53aa-4893-85c7-e36f85a1efad
de Jong, Eiko K.
e669bddc-9d5b-46fc-b3d9-880a2fdf8558
Hoyng, Carel B.
97ec7551-601c-449e-b539-5a476d56cd5d
Cain, Melinda S.
60666c02-1da9-42ab-b695-62c54bf20993
Richardson, Andrea J.
a194ec51-bc26-4f96-a67e-ad37fef5e6e3
Martin, Tammy M.
d4ed6f8c-6de5-4beb-b433-53e70f4c6314
Blangero, John
8dc0636e-04ac-430d-b552-e0c1e8432224
Weeks, Daniel E.
f98f5f10-5aa6-4258-8fd4-3fe60937af5d
Dhillon, Bal
bf394f89-07b5-42c9-8be6-bef9bd5bd9e2
van Duijn, Cornelia M.
27551344-a96f-4537-be37-61edd2d89845
Doheny, Kimberly F.
8bb0edd4-9874-4630-bbbd-854471b840db
Romm, Jane
eeac2384-7fa6-4740-9a92-c21c5dac04df
Klaver, Caroline C.W.
bcfef58f-f6f3-4869-af44-c7ca68400797
Hayward, Caroline
8b58ae74-401a-4306-8b8f-c8414485131c
Gorin, Michael B.
a23a44a9-953c-40c2-8ec4-50ef04ffcb61
Klein, Michael L.
a42eacc1-8a0c-440a-9231-d463570a902b
Baird, Paul N.
e65a0168-2132-4e75-88ef-f76698ec1f4e
den Hollander, Anneke I.
55961992-9080-4986-ae08-f3e680a49b11
Fauser, Sascha
9828d1fc-966e-40e7-a726-ec9913eeabdf
Yates, John R.W.
9095ad1d-3e7a-45a5-96b8-1d91fd275ef5
Allikmets, Rando
77a09273-e325-4586-bbdf-53a7142e97f6
Wang, Jie Jin
f322fd41-2b1c-4959-afa4-6ebd826c4035
Schaumberg, Debra A.
0ba359ef-8c74-48d3-98d6-0969fb56621c
Klein, Barbara E.K.
b81f9d69-81b0-4bff-8217-eb0bab6a267c
Hagstrom, Stephanie A.
b5dd5c35-510b-4230-985c-15a972a6fec7
Chowers, Itay
26b0c0b0-fa65-4004-909b-77215e8a6949
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Léveillard, Thierry
b7379316-c2c2-4f46-b371-58ee85ec5509
Zhang, Kang
286367bb-0902-4d4f-8307-7528da6e67fc
Brilliant, Murray H.
59d3368b-096c-4de9-8b47-2ba85865a3ee
Hewitt, Alex W.
9dffa147-6f00-40df-9f18-95f8552aa140
Swaroop, Anand
57c976d2-16af-4b36-bad5-18243e15fddb
Chew, Emily Y.
576b6aef-071c-4f72-be97-ad83467f258a
Pericak-Vance, Margaret A.
a5e0d7d1-3254-4148-8e9b-719cfe357c8e
DeAngelis, Margaret
a53c8927-b591-4864-9730-da52c1a91573
Stambolian, Dwight
dd84d1fd-db0f-404d-9e05-ea3f776b8446
Haines, Jonathan L.
152169d9-92a1-41f3-8a79-7323f7540e3b
Iyengar, Sudha K.
436a527c-abba-418b-b45e-1548606be86c
Weber, Bernhard H.F.
2d73f4e5-de30-4807-8926-c8f6c1288840
Abecasis, Gonçalo R.
5a59df29-26c9-4e97-b0ba-1a58950e6bc0
Heid, Iris M.
166665f0-ed45-4d07-9019-4f7e933df873
Fritsche, Lars G.
5f2b0f97-1994-4658-baf5-c74dcdab3a2e
Igl, Wilmar
a3722cdf-0a15-4b60-a069-407c5edb52be
Cooke Bailey, Jessica N.
192ad3eb-5f5e-4817-a50d-9ca4ce9720c1
Grassmann, Felix
a72edc86-c7e0-495f-a827-51d7db514076
Sengupta, Sebanti
e095ad27-7e6d-447a-a04d-70297e5ad4a0
Bragg-Gresham, Jennifer L.
70aa0364-24d9-4527-8027-c6f6053d90ce
Burdon, Kathryn P.
34420e05-5749-451e-827c-38e3f36d2f58
Hebbring, Scott J.
beeb0ecf-27c2-4c86-b914-c1aa133fd1c4
Wen, Cindy
1a23ac3a-87f6-492b-8ba1-6f9c3bbb2f04
Gorski, Mathias
b75bf9b7-7456-47cb-93de-1611569e843b
Kim, Ivana K.
555c047a-270b-41ff-9514-0f1c9aed0573
Cho, David
0e28ef93-9b86-4f72-ab9c-1b146f72035d
Zack, Donald
d8106848-2f0f-490f-9339-5ea6716503ae
Souied, Eric
f99aa288-924d-43c9-9f82-6d2eb3f4f6a8
Scholl, Hendrik P.N.
2c38ca3c-90a8-455d-a22c-b52508a9890e
Bala, Elisa
353206a4-c3eb-4e56-93cd-ab7e20d1366e
Lee, Kristine E.
68503d7b-a431-4f51-9bf1-59f2c3bdf5aa
Hunter, David J.
2a7b7bbf-a9cc-4a70-8d2a-fbb169501a14
Sardell, Rebecca J.
a91abc89-3e13-4258-adf4-9944d55cf408
Mitchell, Paul
b2bb46ab-6cd6-44fa-9b4a-b96a50650236
Merriam, Joanna E.
66fe67e6-82a5-4840-b1ef-ea38c3ea92a8
Cipriani, Valentina
df4a538c-6639-45c5-818a-255aa59b44cf
Hoffman, Joshua D.
0081f5ac-e49f-46c5-8b2f-7d45a7ecbc48
Schick, Tina
e42452ef-7716-4037-a135-40b221e447e9
Lechanteur, Yara T.E.
7d0c7c26-818d-4074-b0bd-e0f321f25e6c
Guymer, Robyn H.
ce21dd40-50d0-439a-bb21-b8ad044a721c
Johnson, Matthew P.
6318d310-f146-459e-aa87-a43a1ef7dbc3
Jiang, Yingda
a7ded535-28f3-490e-9889-968a753f32b2
Stanton, Chloe M.
e49a140e-86a0-46f4-a109-fde65288d457
Buitendijk, Gabriëlle H.S.
b7db3a9c-4ec0-487d-a758-221178c60da3
Zhan, Xiaowei
4cf61199-f167-44cf-bc22-3971ee962287
Kwong, Alan M.
d604b200-77eb-431b-bb89-7fe7aaf4ab35
Boleda, Alexis
848ad413-3d6e-45b5-bc32-4b4c535723de
Brooks, Matthew
50228f36-2eda-41f6-b27e-4acbaf8a0a6f
Gieser, Linn
a95498e7-982d-43bc-a83a-e2126a436078
Ratnapriya, Rinki
32da91bd-89f5-4c79-89d9-ff60a3140c96
Branham, Kari E.
c9863a7b-eb01-4523-818e-81752386efd8
Foerster, Johanna R.
7f344fbc-d01e-41d5-b7d4-29cc8306a524
Heckenlively, John R.
c048f769-0ec9-4275-bc54-8cc2a6ec6b05
Othman, Mohammad I.
4e6e5486-b4c3-43b8-a217-96e7456aee7f
Vote, Brendan J.
0a0d04ba-73de-49b9-a244-f959b310a6dc
Liang, Helena Hai
f6b33d3a-73cc-491a-86bb-41fe68353a38
Souzeau, Emmanuelle
005c82f2-d220-4995-b722-bab94749eb9b
McAllister, Ian L.
2a7f95af-8fa8-4c9e-9f51-1729d1d84dce
Isaacs, Timothy
5058b914-d851-446a-a52f-3619f74ba5b0
Hall, Janette
71442469-e771-43f4-a31d-5b05a9247b3d
Lake, Stewart
13e2177f-fb3c-4091-955e-b2c6d7c3162a
Mackey, David A.
b627e9fd-68dd-4473-bfb4-c05d98cdd941
Constable, Ian J.
22679d65-bc32-43ed-bf98-a824fd7b262f
Craig, Jamie E.
795b9c1d-b781-4a27-90ce-cd0ddaa70a9a
Kitchner, Terrie E.
2cbd80e1-1325-4022-9e81-c2ffc97d7c56
Yang, Zhenglin
15c73a06-6c68-4519-b997-7947feb8d588
Su, Zhiguang
392ee7e4-18dd-4aa3-acbd-a2b742eaba45
Luo, Hongrong
41f5d9a3-c480-4ca5-9bf8-ed767df6550b
Chen, Daniel
968712bc-546b-45f9-96f4-4d3627336b38
Ouyang, Hong
80b6393b-e171-4e64-8eb9-89c912321f29
Flagg, Ken
74545534-2bb2-418b-b418-c623fb0c444d
Lin, Danni
ef95c2bf-7bd7-450e-a944-7a8380f32a6d
Mao, Guanping
4477be3d-e529-4145-808f-adf5a917219f
Ferreyra, Henry
5ba787f6-9bfe-4d32-bf63-423e3a3ddcf0
Stark, Klaus
a16b88de-ef50-4cbc-a104-75e0befeae4e
von Strachwitz, Claudia N.
d9087fa4-2455-4c40-a882-87be6fbecb77
Wolf, Armin
bc61d48f-3535-4f40-8a7d-7a13650fe7a3
Brandl, Caroline
4b539276-dcd9-4041-a762-6080a3ae42d9
Rudolph, Guenther
8e26f35f-4331-4bea-97b8-98b008dc42c1
Olden, Matthias
48408f0b-936a-44d3-b7e5-213d5eb60269
Morrison, Margaux A.
6e5f7330-cb0c-466e-9449-fed4374fd3d7
Morgan, Denise J
c6947006-86e4-4ef3-a726-2dc07a20ee03
Schu, Matthew
53413e5b-742f-4b93-86e3-e6862022b371
Ahn, Jeeyun
6de22257-f696-476b-a97f-224f4adbb8e7
Silvestri, Giuliana
8552d5e4-db6e-41b4-857f-967dffcd8712
Tsironi, Evangelia E.
c61bf54a-bcef-4c67-876a-16f7d27def5b
Park, Kyu Hyung
d88b3f1c-81b9-4646-b517-425a717d87e0
Farrer, Lindsay A.
5e0f83bf-3eb9-458a-b750-f1e608499e48
Orlin, Anton
855323dc-11b5-4a11-83b2-b9d0d57a5834
Brucker, Alexander
f59dcc34-3a0f-4cdd-bedb-635e3d9f7b61
Li, Mingyao
81e6fd8b-50cb-4939-8530-f87be479b58c
Curcio, Christine A.
0467a2bc-35aa-471d-864a-f845ffec1ed5
Mohand-Saïd, Saddek
885b25d3-51cc-428e-add2-443e8d712c9a
Sahel, José-Alain
4f3dfd82-08f2-4fac-b46f-43d7c7501857
Audo, Isabelle
6941f4f3-9139-4d9c-ba6c-371fe7eec722
Benchaboune, Mustapha
32094a93-5a9f-4c13-b0e4-806da3cbbdaf
Cree, Angela J.
6724b71b-8828-4abb-971f-0856c2af555e
Rennie, Christina A.
774e5501-a414-47b8-a036-ee3adb226fc2
Goverdhan, Srinivas V.
9ae32d5a-5c82-48a4-962d-1ed8acc3991e
Grunin, Michelle
4a3152f1-9fc1-41ef-ad3f-fb7da4655bbc
Hagbi-Levi, Shira
2c5bfd04-e2a9-492b-ba5b-d58f853c7fbe
Campochiaro, Peter
fdc7fdfe-dba3-4b19-a9bf-fb02659a60cf
Katsanis, Nicholas
84c1ae0d-8198-41c6-91da-07330b39dd0d
Holz, Frank G.
c31bba20-ea0a-4937-ba14-22395fa08f66
Blond, Frédéric
49520eb6-264a-496f-b4ba-b98c7d14235a
Blanché, Hélène
dfa6ea8e-1b32-40c2-8c61-855a685dcc2c
Deleuze, Jean-François
92fd4dc3-0244-4167-8f15-540ad7e1d63d
Igo, Robert P.
c88ecc47-78a4-4b03-980c-542c56cb38b7
Truitt, Barbara
eae91ef1-fe6a-4220-a1a3-cd543a42262f
Peachey, Neal S.
42099a42-cf34-49f9-a686-b481bdedd5a8
Meuer, Stacy M.
77532ffa-a078-43ce-9384-ce64578e48e0
Myers, Chelsea E.
9cdea256-c976-4799-a17d-ca71c3717636
Moore, Emily L.
ef3d0979-8a88-467a-ac67-8d3c05a271c0
Klein, Ronald
3cce2b44-6cd3-4a91-bf9e-bfb9d5764dde
Hauser, Michael A.
7770a8b2-8c45-4d4e-9435-5c239d8b4258
Postel, Eric A.
1b24eb1e-1324-4f88-aa7c-3d3a5b0628d1
Courtenay, Monique D.
eb7de201-5a93-4eb7-89ab-7e6f41433329
Schwartz, Stephen G.
3f642455-f396-4a43-a3e1-6bc67369b942
Kovach, Jaclyn L.
5f781211-a06f-48fe-bbce-adfabd8a522a
Scott, William K.
a59d2b10-185f-4660-a9f4-4af0774bea09
Liew, Gerald
31018dd0-8742-4454-8c5b-70e25580fa15
Tan, Ava G.
92d59a47-43d8-490d-96e2-51b1db1eacfa
Gopinath, Bamini
e5044b3d-92c9-4dc9-bd31-8e527149b2e9
Merriam, John C.
19704ca6-c497-48be-915a-6efbb67b3cb1
Smith, R. Theodore
58d37a6a-a5c0-4906-b60a-6826457ab3fc
Khan, Jane C.
6f6d25de-f390-4cdb-8b3c-ce5e5bce5d9d
Shahid, Humma
f5e43d4f-13e1-4779-af60-f41a93ed6891
Moore, Anthony T.
b354a26a-bed7-4a54-a3ab-32083c425f33
McGrath, J. Allie
d18310bc-3284-4178-83e7-ca553609cc91
Laux, Reneé
c048f4ba-e9b2-4b8f-adc6-4a45b8c80853
Brantley, Milam A.
224a5868-7e26-4319-97f7-242dbaba5c71
Agarwal, Anita
8970b628-caf0-4f2b-b83c-ca29ca9ba2b3
Ersoy, Lebriz
e132d24e-9cad-4681-8e0f-6d33fbbb10dc
Caramoy, Albert
d78d8730-6196-4de8-a0dd-92080860ec30
Langmann, Thomas
0c511bfb-a720-40c3-8d19-ca964ed991cb
Saksens, Nicole T.M.
c69bf85d-53aa-4893-85c7-e36f85a1efad
de Jong, Eiko K.
e669bddc-9d5b-46fc-b3d9-880a2fdf8558
Hoyng, Carel B.
97ec7551-601c-449e-b539-5a476d56cd5d
Cain, Melinda S.
60666c02-1da9-42ab-b695-62c54bf20993
Richardson, Andrea J.
a194ec51-bc26-4f96-a67e-ad37fef5e6e3
Martin, Tammy M.
d4ed6f8c-6de5-4beb-b433-53e70f4c6314
Blangero, John
8dc0636e-04ac-430d-b552-e0c1e8432224
Weeks, Daniel E.
f98f5f10-5aa6-4258-8fd4-3fe60937af5d
Dhillon, Bal
bf394f89-07b5-42c9-8be6-bef9bd5bd9e2
van Duijn, Cornelia M.
27551344-a96f-4537-be37-61edd2d89845
Doheny, Kimberly F.
8bb0edd4-9874-4630-bbbd-854471b840db
Romm, Jane
eeac2384-7fa6-4740-9a92-c21c5dac04df
Klaver, Caroline C.W.
bcfef58f-f6f3-4869-af44-c7ca68400797
Hayward, Caroline
8b58ae74-401a-4306-8b8f-c8414485131c
Gorin, Michael B.
a23a44a9-953c-40c2-8ec4-50ef04ffcb61
Klein, Michael L.
a42eacc1-8a0c-440a-9231-d463570a902b
Baird, Paul N.
e65a0168-2132-4e75-88ef-f76698ec1f4e
den Hollander, Anneke I.
55961992-9080-4986-ae08-f3e680a49b11
Fauser, Sascha
9828d1fc-966e-40e7-a726-ec9913eeabdf
Yates, John R.W.
9095ad1d-3e7a-45a5-96b8-1d91fd275ef5
Allikmets, Rando
77a09273-e325-4586-bbdf-53a7142e97f6
Wang, Jie Jin
f322fd41-2b1c-4959-afa4-6ebd826c4035
Schaumberg, Debra A.
0ba359ef-8c74-48d3-98d6-0969fb56621c
Klein, Barbara E.K.
b81f9d69-81b0-4bff-8217-eb0bab6a267c
Hagstrom, Stephanie A.
b5dd5c35-510b-4230-985c-15a972a6fec7
Chowers, Itay
26b0c0b0-fa65-4004-909b-77215e8a6949
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Léveillard, Thierry
b7379316-c2c2-4f46-b371-58ee85ec5509
Zhang, Kang
286367bb-0902-4d4f-8307-7528da6e67fc
Brilliant, Murray H.
59d3368b-096c-4de9-8b47-2ba85865a3ee
Hewitt, Alex W.
9dffa147-6f00-40df-9f18-95f8552aa140
Swaroop, Anand
57c976d2-16af-4b36-bad5-18243e15fddb
Chew, Emily Y.
576b6aef-071c-4f72-be97-ad83467f258a
Pericak-Vance, Margaret A.
a5e0d7d1-3254-4148-8e9b-719cfe357c8e
DeAngelis, Margaret
a53c8927-b591-4864-9730-da52c1a91573
Stambolian, Dwight
dd84d1fd-db0f-404d-9e05-ea3f776b8446
Haines, Jonathan L.
152169d9-92a1-41f3-8a79-7323f7540e3b
Iyengar, Sudha K.
436a527c-abba-418b-b45e-1548606be86c
Weber, Bernhard H.F.
2d73f4e5-de30-4807-8926-c8f6c1288840
Abecasis, Gonçalo R.
5a59df29-26c9-4e97-b0ba-1a58950e6bc0
Heid, Iris M.
166665f0-ed45-4d07-9019-4f7e933df873

Fritsche, Lars G., Igl, Wilmar, Cooke Bailey, Jessica N., Grassmann, Felix, Sengupta, Sebanti, Bragg-Gresham, Jennifer L., Burdon, Kathryn P., Hebbring, Scott J., Wen, Cindy, Gorski, Mathias, Kim, Ivana K., Cho, David, Zack, Donald, Souied, Eric, Scholl, Hendrik P.N., Bala, Elisa, Lee, Kristine E., Hunter, David J., Sardell, Rebecca J., Mitchell, Paul, Merriam, Joanna E., Cipriani, Valentina, Hoffman, Joshua D., Schick, Tina, Lechanteur, Yara T.E., Guymer, Robyn H., Johnson, Matthew P., Jiang, Yingda, Stanton, Chloe M., Buitendijk, Gabriëlle H.S., Zhan, Xiaowei, Kwong, Alan M., Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki, Branham, Kari E., Foerster, Johanna R., Heckenlively, John R., Othman, Mohammad I., Vote, Brendan J., Liang, Helena Hai, Souzeau, Emmanuelle, McAllister, Ian L., Isaacs, Timothy, Hall, Janette, Lake, Stewart, Mackey, David A., Constable, Ian J., Craig, Jamie E., Kitchner, Terrie E., Yang, Zhenglin, Su, Zhiguang, Luo, Hongrong, Chen, Daniel, Ouyang, Hong, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Stark, Klaus, von Strachwitz, Claudia N., Wolf, Armin, Brandl, Caroline, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A., Morgan, Denise J, Schu, Matthew, Ahn, Jeeyun, Silvestri, Giuliana, Tsironi, Evangelia E., Park, Kyu Hyung, Farrer, Lindsay A., Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A., Mohand-Saïd, Saddek, Sahel, José-Alain, Audo, Isabelle, Benchaboune, Mustapha, Cree, Angela J., Rennie, Christina A., Goverdhan, Srinivas V., Grunin, Michelle, Hagbi-Levi, Shira, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G., Blond, Frédéric, Blanché, Hélène, Deleuze, Jean-François, Igo, Robert P., Truitt, Barbara, Peachey, Neal S., Meuer, Stacy M., Myers, Chelsea E., Moore, Emily L., Klein, Ronald, Hauser, Michael A., Postel, Eric A., Courtenay, Monique D., Schwartz, Stephen G., Kovach, Jaclyn L., Scott, William K., Liew, Gerald, Tan, Ava G., Gopinath, Bamini, Merriam, John C., Smith, R. Theodore, Khan, Jane C., Shahid, Humma, Moore, Anthony T., McGrath, J. Allie, Laux, Reneé, Brantley, Milam A., Agarwal, Anita, Ersoy, Lebriz, Caramoy, Albert, Langmann, Thomas, Saksens, Nicole T.M., de Jong, Eiko K., Hoyng, Carel B., Cain, Melinda S., Richardson, Andrea J., Martin, Tammy M., Blangero, John, Weeks, Daniel E., Dhillon, Bal, van Duijn, Cornelia M., Doheny, Kimberly F., Romm, Jane, Klaver, Caroline C.W., Hayward, Caroline, Gorin, Michael B., Klein, Michael L., Baird, Paul N., den Hollander, Anneke I., Fauser, Sascha, Yates, John R.W., Allikmets, Rando, Wang, Jie Jin, Schaumberg, Debra A., Klein, Barbara E.K., Hagstrom, Stephanie A., Chowers, Itay, Lotery, Andrew J., Léveillard, Thierry, Zhang, Kang, Brilliant, Murray H., Hewitt, Alex W., Swaroop, Anand, Chew, Emily Y., Pericak-Vance, Margaret A., DeAngelis, Margaret, Stambolian, Dwight, Haines, Jonathan L., Iyengar, Sudha K., Weber, Bernhard H.F., Abecasis, Gonçalo R. and Heid, Iris M. (2016) A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nature Genetics, 48 (2), 134-143. (doi:10.1038/ng.3448). (PMID:26691988 )

Record type: Article

Abstract

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Full text not available from this repository.

More information

Accepted/In Press date: 22 October 2015
e-pub ahead of print date: 21 December 2015
Published date: February 2016
Keywords: genome-wide association studies, genomics, neurodegenerative diseases
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 386795
URI: https://eprints.soton.ac.uk/id/eprint/386795
ISSN: 1061-4036
PURE UUID: d5ab8d24-672a-4165-be31-992aef1ecf03
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 04 Feb 2016 14:22
Last modified: 03 Dec 2019 01:50

Export record

Altmetrics

Contributors

Author: Lars G. Fritsche
Author: Wilmar Igl
Author: Jessica N. Cooke Bailey
Author: Felix Grassmann
Author: Sebanti Sengupta
Author: Jennifer L. Bragg-Gresham
Author: Kathryn P. Burdon
Author: Scott J. Hebbring
Author: Cindy Wen
Author: Mathias Gorski
Author: Ivana K. Kim
Author: David Cho
Author: Donald Zack
Author: Eric Souied
Author: Hendrik P.N. Scholl
Author: Elisa Bala
Author: Kristine E. Lee
Author: David J. Hunter
Author: Rebecca J. Sardell
Author: Paul Mitchell
Author: Joanna E. Merriam
Author: Valentina Cipriani
Author: Joshua D. Hoffman
Author: Tina Schick
Author: Yara T.E. Lechanteur
Author: Robyn H. Guymer
Author: Matthew P. Johnson
Author: Yingda Jiang
Author: Chloe M. Stanton
Author: Gabriëlle H.S. Buitendijk
Author: Xiaowei Zhan
Author: Alan M. Kwong
Author: Alexis Boleda
Author: Matthew Brooks
Author: Linn Gieser
Author: Rinki Ratnapriya
Author: Kari E. Branham
Author: Johanna R. Foerster
Author: John R. Heckenlively
Author: Mohammad I. Othman
Author: Brendan J. Vote
Author: Helena Hai Liang
Author: Emmanuelle Souzeau
Author: Ian L. McAllister
Author: Timothy Isaacs
Author: Janette Hall
Author: Stewart Lake
Author: David A. Mackey
Author: Ian J. Constable
Author: Jamie E. Craig
Author: Terrie E. Kitchner
Author: Zhenglin Yang
Author: Zhiguang Su
Author: Hongrong Luo
Author: Daniel Chen
Author: Hong Ouyang
Author: Ken Flagg
Author: Danni Lin
Author: Guanping Mao
Author: Henry Ferreyra
Author: Klaus Stark
Author: Claudia N. von Strachwitz
Author: Armin Wolf
Author: Caroline Brandl
Author: Guenther Rudolph
Author: Matthias Olden
Author: Margaux A. Morrison
Author: Denise J Morgan
Author: Matthew Schu
Author: Jeeyun Ahn
Author: Giuliana Silvestri
Author: Evangelia E. Tsironi
Author: Kyu Hyung Park
Author: Lindsay A. Farrer
Author: Anton Orlin
Author: Alexander Brucker
Author: Mingyao Li
Author: Christine A. Curcio
Author: Saddek Mohand-Saïd
Author: José-Alain Sahel
Author: Isabelle Audo
Author: Mustapha Benchaboune
Author: Angela J. Cree
Author: Christina A. Rennie
Author: Srinivas V. Goverdhan
Author: Michelle Grunin
Author: Shira Hagbi-Levi
Author: Peter Campochiaro
Author: Nicholas Katsanis
Author: Frank G. Holz
Author: Frédéric Blond
Author: Hélène Blanché
Author: Jean-François Deleuze
Author: Robert P. Igo
Author: Barbara Truitt
Author: Neal S. Peachey
Author: Stacy M. Meuer
Author: Chelsea E. Myers
Author: Emily L. Moore
Author: Ronald Klein
Author: Michael A. Hauser
Author: Eric A. Postel
Author: Monique D. Courtenay
Author: Stephen G. Schwartz
Author: Jaclyn L. Kovach
Author: William K. Scott
Author: Gerald Liew
Author: Ava G. Tan
Author: Bamini Gopinath
Author: John C. Merriam
Author: R. Theodore Smith
Author: Jane C. Khan
Author: Humma Shahid
Author: Anthony T. Moore
Author: J. Allie McGrath
Author: Reneé Laux
Author: Milam A. Brantley
Author: Anita Agarwal
Author: Lebriz Ersoy
Author: Albert Caramoy
Author: Thomas Langmann
Author: Nicole T.M. Saksens
Author: Eiko K. de Jong
Author: Carel B. Hoyng
Author: Melinda S. Cain
Author: Andrea J. Richardson
Author: Tammy M. Martin
Author: John Blangero
Author: Daniel E. Weeks
Author: Bal Dhillon
Author: Cornelia M. van Duijn
Author: Kimberly F. Doheny
Author: Jane Romm
Author: Caroline C.W. Klaver
Author: Caroline Hayward
Author: Michael B. Gorin
Author: Michael L. Klein
Author: Paul N. Baird
Author: Anneke I. den Hollander
Author: Sascha Fauser
Author: John R.W. Yates
Author: Rando Allikmets
Author: Jie Jin Wang
Author: Debra A. Schaumberg
Author: Barbara E.K. Klein
Author: Stephanie A. Hagstrom
Author: Itay Chowers
Author: Thierry Léveillard
Author: Kang Zhang
Author: Murray H. Brilliant
Author: Alex W. Hewitt
Author: Anand Swaroop
Author: Emily Y. Chew
Author: Margaret A. Pericak-Vance
Author: Margaret DeAngelis
Author: Dwight Stambolian
Author: Jonathan L. Haines
Author: Sudha K. Iyengar
Author: Bernhard H.F. Weber
Author: Gonçalo R. Abecasis
Author: Iris M. Heid

University divisions

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 https://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.

×