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

L.G. Fritsche, W. Igl, J.N.C. Bailey, F. Grassmann, S. Sengupta, J.L. Bragg-Gresham, K.P. Burdon, S.J. Hebbring, C. Wen, M. Gorski, I.K. Kim, D. Cho, D. Zack, E. Souied, H.P.N. Scholl, E. Bala, K. Elee, D.J. Hunter, R.J. Sardell, P. Mitchell & 56 others J.E. Merriam, V. Cipriani, J.D. Hoffman, T. Schick, Y.T.E. Lechanteur, R.H. Guymer, M.P. Johnson, Y. Jiang, C.M. Stanton, G.H.S. Buitendijk, X. Zhan, A.M. Kwong, A. Boleda, M. Brooks, L. Gieser, R. Ratnapriya, K.E. Branham, J.R. Foerster, J.R. Heckenlively, M.I. Othman, B.J. Vote, H.H. Liang, E. Souzeau, Ian Mcallister, Timothy Isaacs, J. Hall, S. Lake, David Mackey, Ian Constable, J.E. Craig, T.E. Kitchner, Z. Yang, Z. Su, H. Luo, D. Chen, H. Ouyang, K. Flagg, D. Lin, G. Mao, H. Ferreyra, K. Stark, C.N. Von Strachwitz, A. Wolf, C. Brandl, G. Rudolph, M. Olden, M.A. Morrison, D.J. Morgan, M. Schu, J. Ahn, G. Silvestri, E. Etsironi, K.H. Park, L.A. Farrer, A. Orlin, A. Brucker

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Abstract

© 2016 Nature America, Inc. 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
Original languageEnglish
Pages (from-to)134-143
JournalNature Genetics
Volume48
Issue number2
DOIs
Publication statusPublished - 2016

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Genome-Wide Association Study
Macular Degeneration
Blindness
Proteins
Therapeutics

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Fritsche, L. G., Igl, W., Bailey, J. N. C., Grassmann, F., Sengupta, S., Bragg-Gresham, J. L., ... Brucker, A. (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. https://doi.org/10.1038/ng.3448
Fritsche, L.G. ; Igl, W. ; Bailey, J.N.C. ; Grassmann, F. ; Sengupta, S. ; Bragg-Gresham, J.L. ; Burdon, K.P. ; Hebbring, S.J. ; Wen, C. ; Gorski, M. ; Kim, I.K. ; Cho, D. ; Zack, D. ; Souied, E. ; Scholl, H.P.N. ; Bala, E. ; Elee, K. ; Hunter, D.J. ; Sardell, R.J. ; Mitchell, P. ; Merriam, J.E. ; Cipriani, V. ; Hoffman, J.D. ; Schick, T. ; Lechanteur, Y.T.E. ; Guymer, R.H. ; Johnson, M.P. ; Jiang, Y. ; Stanton, C.M. ; Buitendijk, G.H.S. ; Zhan, X. ; Kwong, A.M. ; Boleda, A. ; Brooks, M. ; Gieser, L. ; Ratnapriya, R. ; Branham, K.E. ; Foerster, J.R. ; Heckenlively, J.R. ; Othman, M.I. ; Vote, B.J. ; Liang, H.H. ; Souzeau, E. ; Mcallister, Ian ; Isaacs, Timothy ; Hall, J. ; Lake, S. ; Mackey, David ; Constable, Ian ; Craig, J.E. ; Kitchner, T.E. ; Yang, Z. ; Su, Z. ; Luo, H. ; Chen, D. ; Ouyang, H. ; Flagg, K. ; Lin, D. ; Mao, G. ; Ferreyra, H. ; Stark, K. ; Von Strachwitz, C.N. ; Wolf, A. ; Brandl, C. ; Rudolph, G. ; Olden, M. ; Morrison, M.A. ; Morgan, D.J. ; Schu, M. ; Ahn, J. ; Silvestri, G. ; Etsironi, E. ; Park, K.H. ; Farrer, L.A. ; Orlin, A. ; Brucker, A. / A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. In: Nature Genetics. 2016 ; Vol. 48, No. 2. pp. 134-143.
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Fritsche, LG, Igl, W, Bailey, JNC, Grassmann, F, Sengupta, S, Bragg-Gresham, JL, Burdon, KP, Hebbring, SJ, Wen, C, Gorski, M, Kim, IK, Cho, D, Zack, D, Souied, E, Scholl, HPN, Bala, E, Elee, K, Hunter, DJ, Sardell, RJ, Mitchell, P, Merriam, JE, Cipriani, V, Hoffman, JD, Schick, T, Lechanteur, YTE, Guymer, RH, Johnson, MP, Jiang, Y, Stanton, CM, Buitendijk, GHS, Zhan, X, Kwong, AM, Boleda, A, Brooks, M, Gieser, L, Ratnapriya, R, Branham, KE, Foerster, JR, Heckenlively, JR, Othman, MI, Vote, BJ, Liang, HH, Souzeau, E, Mcallister, I, Isaacs, T, Hall, J, Lake, S, Mackey, D, Constable, I, Craig, JE, Kitchner, TE, Yang, Z, Su, Z, Luo, H, Chen, D, Ouyang, H, Flagg, K, Lin, D, Mao, G, Ferreyra, H, Stark, K, Von Strachwitz, CN, Wolf, A, Brandl, C, Rudolph, G, Olden, M, Morrison, MA, Morgan, DJ, Schu, M, Ahn, J, Silvestri, G, Etsironi, E, Park, KH, Farrer, LA, Orlin, A & Brucker, A 2016, 'A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants' Nature Genetics, vol. 48, no. 2, pp. 134-143. https://doi.org/10.1038/ng.3448

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. / Fritsche, L.G.; Igl, W.; Bailey, J.N.C.; Grassmann, F.; Sengupta, S.; Bragg-Gresham, J.L.; Burdon, K.P.; Hebbring, S.J.; Wen, C.; Gorski, M.; Kim, I.K.; Cho, D.; Zack, D.; Souied, E.; Scholl, H.P.N.; Bala, E.; Elee, K.; Hunter, D.J.; Sardell, R.J.; Mitchell, P.; Merriam, J.E.; Cipriani, V.; Hoffman, J.D.; Schick, T.; Lechanteur, Y.T.E.; Guymer, R.H.; Johnson, M.P.; Jiang, Y.; Stanton, C.M.; Buitendijk, G.H.S.; Zhan, X.; Kwong, A.M.; Boleda, A.; Brooks, M.; Gieser, L.; Ratnapriya, R.; Branham, K.E.; Foerster, J.R.; Heckenlively, J.R.; Othman, M.I.; Vote, B.J.; Liang, H.H.; Souzeau, E.; Mcallister, Ian; Isaacs, Timothy; Hall, J.; Lake, S.; Mackey, David; Constable, Ian; Craig, J.E.; Kitchner, T.E.; Yang, Z.; Su, Z.; Luo, H.; Chen, D.; Ouyang, H.; Flagg, K.; Lin, D.; Mao, G.; Ferreyra, H.; Stark, K.; Von Strachwitz, C.N.; Wolf, A.; Brandl, C.; Rudolph, G.; Olden, M.; Morrison, M.A.; Morgan, D.J.; Schu, M.; Ahn, J.; Silvestri, G.; Etsironi, E.; Park, K.H.; Farrer, L.A.; Orlin, A.; Brucker, A.

In: Nature Genetics, Vol. 48, No. 2, 2016, p. 134-143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

AU - Fritsche, L.G.

AU - Igl, W.

AU - Bailey, J.N.C.

AU - Grassmann, F.

AU - Sengupta, S.

AU - Bragg-Gresham, J.L.

AU - Burdon, K.P.

AU - Hebbring, S.J.

AU - Wen, C.

AU - Gorski, M.

AU - Kim, I.K.

AU - Cho, D.

AU - Zack, D.

AU - Souied, E.

AU - Scholl, H.P.N.

AU - Bala, E.

AU - Elee, K.

AU - Hunter, D.J.

AU - Sardell, R.J.

AU - Mitchell, P.

AU - Merriam, J.E.

AU - Cipriani, V.

AU - Hoffman, J.D.

AU - Schick, T.

AU - Lechanteur, Y.T.E.

AU - Guymer, R.H.

AU - Johnson, M.P.

AU - Jiang, Y.

AU - Stanton, C.M.

AU - Buitendijk, G.H.S.

AU - Zhan, X.

AU - Kwong, A.M.

AU - Boleda, A.

AU - Brooks, M.

AU - Gieser, L.

AU - Ratnapriya, R.

AU - Branham, K.E.

AU - Foerster, J.R.

AU - Heckenlively, J.R.

AU - Othman, M.I.

AU - Vote, B.J.

AU - Liang, H.H.

AU - Souzeau, E.

AU - Mcallister, Ian

AU - Isaacs, Timothy

AU - Hall, J.

AU - Lake, S.

AU - Mackey, David

AU - Constable, Ian

AU - Craig, J.E.

AU - Kitchner, T.E.

AU - Yang, Z.

AU - Su, Z.

AU - Luo, H.

AU - Chen, D.

AU - Ouyang, H.

AU - Flagg, K.

AU - Lin, D.

AU - Mao, G.

AU - Ferreyra, H.

AU - Stark, K.

AU - Von Strachwitz, C.N.

AU - Wolf, A.

AU - Brandl, C.

AU - Rudolph, G.

AU - Olden, M.

AU - Morrison, M.A.

AU - Morgan, D.J.

AU - Schu, M.

AU - Ahn, J.

AU - Silvestri, G.

AU - Etsironi, E.

AU - Park, K.H.

AU - Farrer, L.A.

AU - Orlin, A.

AU - Brucker, A.

PY - 2016

Y1 - 2016

N2 - © 2016 Nature America, Inc. 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

AB - © 2016 Nature America, Inc. 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

U2 - 10.1038/ng.3448

DO - 10.1038/ng.3448

M3 - Article

VL - 48

SP - 134

EP - 143

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -