Universität zu Köln

Riaz, Moeen, Lores-Motta, Laura ORCID: 0000-0002-2423-9126, Richardson, Andrea J., Lu, Yi ORCID: 0000-0001-9933-3654, Montgomery, Grant, Omar, Amer ORCID: 0000-0003-1520-392X, Koenekoop, Robert K., Chen, John, Muether, Philipp, Altay, Lebriz, Schick, Tina, Fauser, Sascha, Smailhodzic, Dzenita, van Asten, Freekje ORCID: 0000-0002-8141-4234, de Jong, Eiko K., Hoyng, Carel B., Burdon, Kathryn P., MacGregor, Stuart, Guymer, Robyn H., den Hollander, Anneke I. and Baird, Paul N. (2016). GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated neovascular age-related macular degeneration (nAMD) patients. We performed pooled DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina 4.3 M array. Primary outcome was change in VA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 6 months of anti-VEGF treatment (patients who lost >= 5 ETDRS letters classified as non-responders and all remaining classified as responders). GWAS analysis identified 44 SNPs of interest: 37 with strong evidence of association (p < 9 x 10(-8)), 2 in drug resistance genes (p < 5 x 10(-6)) and 5 nonsynonymous changes (p < 1 x 10(-4)). In the validation phase, individual genotyping of 44 variants showed three SNPs (rs4910623 p = 5.6 x 10(-5), rs323085 p = 6.5 x 10(-4) and rs10198937 p = 1.30 x 10(-3)) remained associated with VA response at 6 months. SNP rs4910623 also associated with treatment response at 3 months (p = 1.5 x 10(-3)). Replication of these three SNPs in 376 patients revealed association of rs4910623 with poor VA response after 3 and 6 months of treatment (p = 2.4 x 10(-3) and p = 3.5 x 10(-2), respectively). Meta-analysis of both cohorts (673 samples) confirmed association of rs4910623 with poor VA response after 3 months (p = 1.2 x 10(-5)) and 6 months (p = 9.3 x 10(-6)) of treatment in nAMD patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Riaz, Moeen UNSPECIFIED UNSPECIFIED UNSPECIFIED Lores-Motta, Laura UNSPECIFIED orcid.org/0000-0002-2423-9126 UNSPECIFIED Richardson, Andrea J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lu, Yi UNSPECIFIED orcid.org/0000-0001-9933-3654 UNSPECIFIED Montgomery, Grant UNSPECIFIED UNSPECIFIED UNSPECIFIED Omar, Amer UNSPECIFIED orcid.org/0000-0003-1520-392X UNSPECIFIED Koenekoop, Robert K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, John UNSPECIFIED UNSPECIFIED UNSPECIFIED Muether, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Altay, Lebriz UNSPECIFIED UNSPECIFIED UNSPECIFIED Schick, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Smailhodzic, Dzenita UNSPECIFIED UNSPECIFIED UNSPECIFIED van Asten, Freekje UNSPECIFIED orcid.org/0000-0002-8141-4234 UNSPECIFIED de Jong, Eiko K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burdon, Kathryn P. UNSPECIFIED UNSPECIFIED UNSPECIFIED MacGregor, Stuart UNSPECIFIED UNSPECIFIED UNSPECIFIED Guymer, Robyn H. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baird, Paul N. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-255401
DOI:	10.1038/srep37924
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; ENDOTHELIAL GROWTH-FACTOR; RANIBIZUMAB; SUSCEPTIBILITY; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25540