Genetic Risk, Lifestyle, and Age-Related Macular Degeneration in Europe
| Autor: | A C C Coolen, Audrey Cougnard-Gregoire, Marius Ueffing, Timo Verzijden, Johanna M. Colijn, Bénédicte M. J. Merle, Hans-Werner Hense, Rufino Silva, Sascha Fauser, Carel B. Hoyng, Catherine Creuzot-Garcher, Caroline C W Klaver, Magda A. Meester-Smoor, Anneke I. den Hollander, Anita de Breuk, Cécile Delcourt |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
medicine.medical_specialty education.field_of_study business.industry Population Single-nucleotide polymorphism Disease Macular degeneration medicine.disease eye diseases 3. Good health Minor allele frequency 03 medical and health sciences Ophthalmology 0302 clinical medicine Internal medicine Epidemiology 030221 ophthalmology & optometry medicine Genetic risk education business 030304 developmental biology Cohort study |
| Zdroj: | Ophthalmology. 128:1039-1049 |
| ISSN: | 0161-6420 |
| Popis: | 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 β 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. |
| Databáze: | OpenAIRE |
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