Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

International AMD Genomics Consortium (IAMDGC)

doi:10.1534/genetics.116.195966

Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

International AMD Genomics Consortium (IAMDGC)

Medical Sciences

University of Regensburg

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

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Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 10 × 10^-773 and 6.7 × 10^-5. This now allows prioritization of the gene of interest for subsequent functional studies.

Original language	English
Pages (from-to)	919-924
Number of pages	6
Journal	Genetics
Volume	205
Issue number	2
Early online date	2 Feb 2017
DOIs	https://doi.org/10.1534/genetics.116.195966
Publication status	Published - Feb 2017

Bibliographical note

The authors thank Paul N. Baird (Ocular Genetics Unit, Centre for Eye Research, Australia) for critically reading the manuscript. The work was funded in part by grants from the German Federal Ministry of Education and Research (BMBF 01ER1206 and 01ER1507) to I.M.H., by the institutional budget for Research and Teaching from the Freestate of Bavaria and the German Research Foundation (WE 1259/19-2) to BHFW.

Keywords

Age-related macular degeneration
ARMS2/HTRA1 gene locus
Genetic association studies
Haplotypes
Linkage disequilibrium

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@article{54d62126d3554339ad8740b392483d9e,

title = "Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration",

abstract = "Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 10 × 10-773 and 6.7 × 10-5. This now allows prioritization of the gene of interest for subsequent functional studies.",

keywords = "Age-related macular degeneration, ARMS2/HTRA1 gene locus, Genetic association studies, Haplotypes, Linkage disequilibrium",

author = "Felix Grassmann and Heid, {Iris M.} and Weber, {Bernhard H.F.} and Fritsche, {L. G.} and W. Igl and Bailey, {J. N.} and S. Sengupta and Bragg-Gresham, {J. L.} and Burdon, {K. P.} and Hebbring, {S. J.} and C. Wen and M. Gorski and Kim, {I. K.} and D. Cho and D. Zack and E. Souied and Scholl, {H. P.} and E. Bala and Lee, {K. E.} and Hunter, {D. J.} and Sardell, {R. J.} and P. Mitchell and Merriam, {J. E.} and V. Cipriani and Hoffman, {J. D.} and T. Schick and Lechanteur, {Y. T.} and Guymer, {R. H.} and Johnson, {M. P.} and Y. Jiang and Stanton, {C. M.} and Buitendijk, {G. H.} and X. Zhan and Kwong, {A. M.} and A. Boleda and M. Brooks and L. Gieser and R. Ratnapriya and Branham, {K. E.} and Foerster, {J. R.} and Heckenlively, {J. R.} and Othman, {M. I.} and Vote, {B. J.} and Liang, {H. H.} and E. Souzeau and McAllister, {I. L.} and T. Isaacs and J. Hall and S. Lake and {International AMD Genomics Consortium (IAMDGC)}",

note = "The authors thank Paul N. Baird (Ocular Genetics Unit, Centre for Eye Research, Australia) for critically reading the manuscript. The work was funded in part by grants from the German Federal Ministry of Education and Research (BMBF 01ER1206 and 01ER1507) to I.M.H., by the institutional budget for Research and Teaching from the Freestate of Bavaria and the German Research Foundation (WE 1259/19-2) to BHFW. ",

year = "2017",

month = feb,

doi = "10.1534/genetics.116.195966",

language = "English",

volume = "205",

pages = "919--924",

journal = "Genetics",

issn = "0016-6731",

publisher = "Oxford University Press (OUP)",

number = "2",

}

TY - JOUR

T1 - Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

AU - Grassmann, Felix

AU - Heid, Iris M.

AU - Weber, Bernhard H.F.

AU - Fritsche, L. G.

AU - Igl, W.

AU - Bailey, J. N.

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.

AU - Bala, E.

AU - Lee, K. E.

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.

AU - Guymer, R. H.

AU - Johnson, M. P.

AU - Jiang, Y.

AU - Stanton, C. M.

AU - Buitendijk, G. H.

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, I. L.

AU - Isaacs, T.

AU - Hall, J.

AU - Lake, S.

AU - International AMD Genomics Consortium (IAMDGC)

N1 - The authors thank Paul N. Baird (Ocular Genetics Unit, Centre for Eye Research, Australia) for critically reading the manuscript. The work was funded in part by grants from the German Federal Ministry of Education and Research (BMBF 01ER1206 and 01ER1507) to I.M.H., by the institutional budget for Research and Teaching from the Freestate of Bavaria and the German Research Foundation (WE 1259/19-2) to BHFW.

PY - 2017/2

Y1 - 2017/2

N2 - Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 10 × 10-773 and 6.7 × 10-5. This now allows prioritization of the gene of interest for subsequent functional studies.

AB - Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 10 × 10-773 and 6.7 × 10-5. This now allows prioritization of the gene of interest for subsequent functional studies.

KW - Age-related macular degeneration

KW - ARMS2/HTRA1 gene locus

KW - Genetic association studies

KW - Haplotypes

KW - Linkage disequilibrium

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U2 - 10.1534/genetics.116.195966

DO - 10.1534/genetics.116.195966

M3 - Article

C2 - 27879347

AN - SCOPUS:85020305656

SN - 0016-6731

VL - 205

SP - 919

EP - 924

JO - Genetics

JF - Genetics

IS - 2

ER -

Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

Abstract

Bibliographical note

Keywords

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