Universität zu Köln

Schick, Tina, Lores-Motta, Laura, Altay, Lebriz, Fritsche, Lars G., den Hollander, Anneke, I and Fauser, Sascha (2020). The Effect of Genetic Variants Associated With Age-Related Macular Degeneration Varies With Age. Invest. Ophthalmol. Vis. Sci., 61 (14). ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. The prevalence of age-related macular degeneration (AMD) increases dramatically with age. This large collaborative study investigates the effects of 51 late-AMD-associated genetic variants in different ages, focusing on individuals above the age of 90 years. METHODS. The study included 27,996 individuals of the International AMD Genomics Consortium; 14,539 showed late AMD (51.9%) and 13,457 were controls (48.1%). Four age groups were compiled: 60 to 69 years, n = 6514, AMD = 2210 (33.9%); 70 to 79 years, n = 12228, AMD = 6217 (51.7%); 80 to 89 years, n = 8285, AMD = 5326 (64.3%); and >= 90 years, n = 969, AMD = 686 (70.8%). The effect sizes of 51 AMD-associated genetic variants were calculated for all age groups and were compared among the age groups. RESULTS. Six variants were associated with late AMD in individuals >= 90 years of age (P <= 0.0006). For rs10922109 and rs570618 (both in CFH), the minor allele (MA) was protective, and minor allele frequency (MAF) increased with age in cases and controls. For rs116503776 in C2/CFB/SKIV2L, the MA was protective, and MAF increased in cases. For rs3750846 in ARMS2/HTRA1, the MA increased risk, and MAF was lower in cases with increasing age. For rs6565597 in NPLOC4/TSPAN10, the MA increased risk. For rs5754227 in SYN3/TIMP3, the MA was protective, and there was no consistent variation in MAF with age. Variants in CFH and ARMS2 showed lower effect sizes at greater age. Interaction analysis showed strong age-related effects for rs570618 (P = 2.24 x 10(-7)) and rs3750846 (P = 0.001). Total genetic risk was lower in individuals >= 90 years old (area under the curve [AUC], 0.795) than in those 70 to 79 years old (AUC, 0.831; P = 0.03) CONCLUSIONS. Effect sizes and MAF of genetic risk factors for late AMD differed among the age groups. These results could guide future work on AMD risk assessment in older individuals.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schick, Tina UNSPECIFIED UNSPECIFIED UNSPECIFIED Lores-Motta, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Altay, Lebriz UNSPECIFIED UNSPECIFIED UNSPECIFIED Fritsche, Lars G. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke, I UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-309154
DOI:	10.1167/iovs.61.14.17
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	61
Number:	14
Date:	2020
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RISK-FACTORS; PREVALENCE; PROGRESSION; MORTALITY Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30915