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; 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

doi:10.1038/ng.3448

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. MitchellJ.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

Centre for Ophthalmology and Visual Science (affiliated with the Lions Eye Institute)

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932 Citations (Scopus)

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 language	English
Pages (from-to)	134-143
Number of pages	10
Journal	Nature Genetics
Volume	48
Issue number	2
DOIs	https://doi.org/10.1038/ng.3448
Publication status	Published - 1 Feb 2016

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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., ... 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

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abstract = "{\textcopyright} 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",

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

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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

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 - 2016/2/1

Y1 - 2016/2/1

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

C2 - 26691988

SN - 1061-4036

VL - 48

SP - 134

EP - 143

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract

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