Fritsche, Lars G., Igl, Wilmar, Bailey, Jessica N. Cooke, Grassmann, Felix ORCID: 0000-0003-1390-7528, 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 ORCID: 0000-0002-0839-9955, Hoffman, Joshua D., Schick, Tina, Lechanteur, Yara T. E., Guymer, Robyn H., Johnson, Matthew P., Jiang, Yingda, Stanton, Chloe M., Buitendijk, Gabrielle H. S., Zhan, Xiaowei, Kwong, Alan M., Boleda, Alexis, Brooks, Matthew, Gieser, Linn, Ratnapriya, Rinki ORCID: 0000-0002-0469-4631, Branham, Kari E., Foerster, Johanna R., Heckenlively, John R., Othman, Mohammad I., Vote, Brendan J., Liang, Helena Hai, Souzeau, Emmanuelle ORCID: 0000-0002-2015-6577, 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 ORCID: 0000-0001-8635-9310, Luo, Hongrong, Chen, Daniel, Flagg, Ken, Lin, Danni, Mao, Guanping, Ferreyra, Henry, Starke, Klaus, von Strachwitz, Claudia N., Wolf, Armin, Brandl, Caroline ORCID: 0000-0001-8223-6137, Rudolph, Guenther, Olden, Matthias, Morrison, Margaux A., Morgan, Denise J., Schu, Matthew, Ahn, Jeeyun ORCID: 0000-0001-9017-1652, Silvestri, Giuliana, Tsironi, Evangelia E., Park, Kyu Hyung, Farrer, Lindsay A., Orlin, Anton, Brucker, Alexander, Li, Mingyao, Curcio, Christine A., Mohand-Said, Saddek, Sahel, Jose-Main, Audo, Isabelle ORCID: 0000-0003-0698-5309, Benchaboune, Mustapha, Cree, Angela J., Rennie, Christina A., Goverdhan, Srinivas V., Grunin, Michelle ORCID: 0000-0002-3155-2858, Hagbi-Levi, Shira ORCID: 0000-0002-2891-0079, Campochiaro, Peter, Katsanis, Nicholas, Holz, Frank G., Blond, Frederic, Blanche, Helene, Deleuze, Jean-Francois, Igo, Robert P., Jr., 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 ORCID: 0000-0003-3573-359X, Merriam, John C., Smith, R. Theodore, Khan, Jane C., Shahid, Humma, Moore, Anthony T., McGrath, J. Allie, Laux, Renee, Brantley, Milam A., Jr., 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 ORCID: 0000-0001-6250-5723, 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 ORCID: 0000-0001-9491-4898, Schaumberg, Debra A., Klein, Barbara E. K., Hagstrom, Stephanie A., Chowers, Itay, Lotery, Andrew J., Leveillard, Thierry ORCID: 0000-0001-5692-8770, Zhang, Kang ORCID: 0000-0002-4549-1697, 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, Goncalo 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 Genet., 48 (2). S. 134 - 144. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

Full text not available from this repository.

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 x 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 x 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fritsche, Lars G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Igl, WilmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bailey, Jessica N. CookeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grassmann, FelixUNSPECIFIEDorcid.org/0000-0003-1390-7528UNSPECIFIED
Sengupta, SebantiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bragg-Gresham, Jennifer L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burdon, Kathryn P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hebbring, Scott J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wen, CindyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gorski, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Ivana K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cho, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zack, DonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Souied, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholl, Hendrik P. N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bala, ElisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Kristine E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunter, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sardell, Rebecca J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merriam, Joanna E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cipriani, ValentinaUNSPECIFIEDorcid.org/0000-0002-0839-9955UNSPECIFIED
Hoffman, Joshua D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schick, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lechanteur, Yara T. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guymer, Robyn H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, Matthew P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, YingdaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stanton, Chloe M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buitendijk, Gabrielle H. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhan, XiaoweiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwong, Alan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boleda, AlexisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gieser, LinnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ratnapriya, RinkiUNSPECIFIEDorcid.org/0000-0002-0469-4631UNSPECIFIED
Branham, Kari E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foerster, Johanna R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heckenlively, John R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Othman, Mohammad I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vote, Brendan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liang, Helena HaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Souzeau, EmmanuelleUNSPECIFIEDorcid.org/0000-0002-2015-6577UNSPECIFIED
McAllister, Ian L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isaacs, TimothyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, JanetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lake, StewartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mackey, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Constable, Ian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Craig, Jamie E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kitchner, Terrie E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, ZhenglinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Su, ZhiguangUNSPECIFIEDorcid.org/0000-0001-8635-9310UNSPECIFIED
Luo, HongrongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flagg, KenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lin, DanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mao, GuanpingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferreyra, HenryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Starke, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Strachwitz, Claudia N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, ArminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandl, CarolineUNSPECIFIEDorcid.org/0000-0001-8223-6137UNSPECIFIED
Rudolph, GuentherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olden, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morrison, Margaux A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, Denise J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schu, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahn, JeeyunUNSPECIFIEDorcid.org/0000-0001-9017-1652UNSPECIFIED
Silvestri, GiulianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsironi, Evangelia E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Kyu HyungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farrer, Lindsay A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orlin, AntonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brucker, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, MingyaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curcio, Christine A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mohand-Said, SaddekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahel, Jose-MainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Audo, IsabelleUNSPECIFIEDorcid.org/0000-0003-0698-5309UNSPECIFIED
Benchaboune, MustaphaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cree, Angela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rennie, Christina A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goverdhan, Srinivas V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grunin, MichelleUNSPECIFIEDorcid.org/0000-0002-3155-2858UNSPECIFIED
Hagbi-Levi, ShiraUNSPECIFIEDorcid.org/0000-0002-2891-0079UNSPECIFIED
Campochiaro, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katsanis, NicholasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holz, Frank G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blond, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanche, HeleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deleuze, Jean-FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Igo, Robert P., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Truitt, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peachey, Neal S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meuer, Stacy M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Myers, Chelsea E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, Emily L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauser, Michael A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Postel, Eric A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Courtenay, Monique D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwartz, Stephen G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kovach, Jaclyn L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scott, William K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liew, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Ava G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gopinath, BaminiUNSPECIFIEDorcid.org/0000-0003-3573-359XUNSPECIFIED
Merriam, John C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smith, R. TheodoreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, Jane C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shahid, HummaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, Anthony T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGrath, J. AllieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laux, ReneeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brantley, Milam A., Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agarwal, AnitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ersoy, LebrizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caramoy, AlbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langmann, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saksens, Nicole T. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Jong, Eiko K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyng, Carel B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cain, Melinda S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richardson, Andrea J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, Tammy M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blangero, JohnUNSPECIFIEDorcid.org/0000-0001-6250-5723UNSPECIFIED
Weeks, Daniel E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dhillon, BalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Duijn, Cornelia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doheny, Kimberly F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romm, JaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klaver, Caroline C. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hayward, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gorin, Michael B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Michael L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baird, Paul N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
den Hollander, Anneke I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fauser, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yates, John R. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allikmets, RandoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, Jie JinUNSPECIFIEDorcid.org/0000-0001-9491-4898UNSPECIFIED
Schaumberg, Debra A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, Barbara E. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hagstrom, Stephanie A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chowers, ItayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lotery, Andrew J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leveillard, ThierryUNSPECIFIEDorcid.org/0000-0001-5692-8770UNSPECIFIED
Zhang, KangUNSPECIFIEDorcid.org/0000-0002-4549-1697UNSPECIFIED
Brilliant, Murray H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hewitt, Alex W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swaroop, AnandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chew, Emily Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pericak-Vance, Margaret A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
DeAngelis, MargaretUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stambolian, DwightUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haines, Jonathan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iyengar, Sudha K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Bernhard H. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abecasis, Goncalo R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heid, Iris M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-286591
DOI: 10.1038/ng.3448
Journal or Publication Title: Nature Genet.
Volume: 48
Number: 2
Page Range: S. 134 - 144
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SEQUENCING IDENTIFIES RARE; BODY-MASS INDEX; HIGH-RISK; SUSCEPTIBILITY LOCI; DISEASE; GENE; MUTATION; BIOLOGY; OSTEOARTHRITIS; METAANALYSISMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28659

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item