Universität zu Köln

Colijn, Johanna M., Meester-Smoor, Magda, Verzijden, Timo, de Breuk, Anita ORCID: 0000-0001-7072-1928, Silva, Rufino ORCID: 0000-0001-8676-0833, Merle, Benedicte M. J., Cougnard-Gregoire, Audrey, Hoyng, Carel B., Fauser, Sascha, Coolen, Anthonius, Creuzot-Garcher, Catherine, Hense, Hans-Werner, Ueffing, Marius, Delcourt, Cecile ORCID: 0000-0002-2099-0481, den Hollander, Anneke, I and Klaver, Caroline C. W. (2021). Genetic Risk, Lifestyle, and Age-Related Macular Degeneration in Europe The EYE-RISK Consortium. Ophthalmology, 128 (7). S. 1039 - 1050. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1549-4713

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Abstract

Purpose: Age-related macular degeneration (AMD) is a common multifactorial disease in the elderly with a prominent genetic basis. Many risk variants have been identified, but the interpretation remains challenging. We investigated the genetic distribution of AMD-associated risk variants in a large European consortium, calculated attributable and pathway-specific genetic risks, and assessed the influence of lifestyle on genetic outcomes. Design: Pooled analysis of cross-sectional data from the European Eye Epidemiology Consortium. Participants: Seventeen thousand one hundred seventy-four individuals 45 years of age or older participating in 6 population-based cohort studies, 2 clinic-based studies, and 1 case-control study. Methods: Age-related macular degeneration was diagnosed and graded based on fundus photographs. Data on genetics, lifestyle, and diet were harmonized. Minor allele frequencies and population-attributable fraction (PAF) were calculated. A total genetic risk score (GRS) and pathway-specific risk scores (complement, lipid, extra-cellular matrix, other) were constructed based on the dosage of SNPs and conditional beta values; a lifestyle score was constructed based on smoking and diet. Main Outcome Measures: Intermediate and late AMD. Results: The risk variants with the largest difference between late AMD patients and control participants and the highest PAFs were located in ARMS2 (rs3750846) and CHF (rs570618 and rs10922109). Combining all genetic variants, the total genetic risk score ranged from -3.50 to 4.63 and increased with AMD severity. Of the late AMD patients, 1581 of 1777 (89%) showed a positive total GRS. The complement pathway and ARMS2 were by far the most prominent genetic pathways contributing to late AMD (positive GRS, 90% of patients with late disease), but risk in 3 pathways was most frequent (35% of patients with late disease). Lifestyle was a strong determinant of the outcome in each genetic risk category; unfavorable lifestyle increased the risk of late AMD at least 2-fold. Conclusions: Genetic risk variants contribute to late AMD in most patients. However, lifestyle factors have a strong influence on the outcome of genetic risk and should be a strong focus in patient management. Genetic risks in ARMS2 and the complement pathway are present in most late AMD patients but are mostly combined with risks in other pathways. (C) 2020 by the American Academy of Ophthalmology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Colijn, Johanna M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meester-Smoor, Magda UNSPECIFIED UNSPECIFIED UNSPECIFIED Verzijden, Timo UNSPECIFIED UNSPECIFIED UNSPECIFIED de Breuk, Anita UNSPECIFIED orcid.org/0000-0001-7072-1928 UNSPECIFIED Silva, Rufino UNSPECIFIED orcid.org/0000-0001-8676-0833 UNSPECIFIED Merle, Benedicte M. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cougnard-Gregoire, Audrey UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Coolen, Anthonius UNSPECIFIED UNSPECIFIED UNSPECIFIED Creuzot-Garcher, Catherine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hense, Hans-Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Ueffing, Marius UNSPECIFIED UNSPECIFIED UNSPECIFIED Delcourt, Cecile UNSPECIFIED orcid.org/0000-0002-2099-0481 UNSPECIFIED den Hollander, Anneke, I UNSPECIFIED UNSPECIFIED UNSPECIFIED Klaver, Caroline C. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-603058
DOI:	10.1016/j.ophtha.2020.11.024
Journal or Publication Title:	Ophthalmology
Volume:	128
Number:	7
Page Range:	S. 1039 - 1050
Date:	2021
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1549-4713
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CIGARETTE-SMOKING; COMPLEMENT-SYSTEM; ASSOCIATION; OMEGA-3-FATTY-ACIDS; PREVALENCE; RARE Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60305