Population Differences in Genetic Risk for Age-Related Macular Degeneration and Implications for Genetic Testing

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

Download Full-text

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

Life ◽

10.3390/life11070635 ◽

2021 ◽

Vol 11 (7) ◽

pp. 635

Author(s):

Monica L. Hu ◽

Joel Quinn ◽

Kanmin Xue

Keyword(s):

Risk Factor ◽

Apolipoprotein E ◽

Macular Degeneration ◽

Amyloid Beta ◽

Complement System ◽

Genetic Risk ◽

Age Related Macular Degeneration ◽

Age Related ◽

Retinal Inflammation ◽

The Complement System

Age-related macular degeneration (AMD) is a multifactorial retinal disorder that is a major global cause of severe visual impairment. The development of an effective therapy to treat geographic atrophy, the predominant form of AMD, remains elusive due to the incomplete understanding of its pathogenesis. Central to AMD diagnosis and pathology are the hallmark lipid and proteinaceous deposits, drusen and reticular pseudodrusen, that accumulate in the subretinal pigment epithelium and subretinal spaces, respectively. Age-related changes and environmental stressors, such as smoking and a high-fat diet, are believed to interact with the many genetic risk variants that have been identified in several major biochemical pathways, including lipoprotein metabolism and the complement system. The APOE gene, encoding apolipoprotein E (APOE), is a major genetic risk factor for AMD, with the APOE2 allele conferring increased risk and APOE4 conferring reduced risk, in comparison to the wildtype APOE3. Paradoxically, APOE4 is the main genetic risk factor in Alzheimer's disease, a disease with features of neuroinflammation and amyloid-beta deposition in common with AMD. The potential interactions of APOE with the complement system and amyloid-beta are discussed here to shed light on their roles in AMD pathogenesis, including in drusen biogenesis, immune cell activation and recruitment, and retinal inflammation.

Download Full-text

Association Between Vitamin D Status and Age-Related Macular Degeneration by Genetic Risk

JAMA Ophthalmology ◽

10.1001/jamaophthalmol.2015.2715 ◽

2015 ◽

Vol 133 (10) ◽

pp. 1171 ◽

Cited By ~ 24

Author(s):

Amy E. Millen ◽

Kristin J. Meyers ◽

Zhe Liu ◽

Corinne D. Engelman ◽

Robert B. Wallace ◽

...

Keyword(s):

Vitamin D ◽

Macular Degeneration ◽

Genetic Risk ◽

Age Related Macular Degeneration ◽

Vitamin D Status ◽

Age Related

Download Full-text

Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-311673 ◽

2018 ◽

Vol 102 (12) ◽

pp. 1691-1695 ◽

Cited By ~ 5

Author(s):

Emma Connolly ◽

Maedbh Rhatigan ◽

Aisling M O’Halloran ◽

Katherine Alyson Muldrew ◽

Usha Chakravarthy ◽

...

Keyword(s):

Risk Factors ◽

Macular Degeneration ◽

Disease Progression ◽

Genetic Risk ◽

Risk Allele ◽

Genetic Risk Factors ◽

Age Related Macular Degeneration ◽

Complement Factor ◽

Age Related ◽

Soft Drusen

Background/aimsAge-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland.MethodsPrevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression.ResultsOlder age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline.ConclusionsThe prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.

Download Full-text

Distinct Genetic Risk Profile of the Rapidly Progressing Diffuse-Trickling Subtype of Geographic Atrophy in Age-Related Macular Degeneration (AMD)

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.15-18593 ◽

2016 ◽

Vol 57 (6) ◽

pp. 2463 ◽

Cited By ~ 6

Author(s):

Monika Fleckenstein ◽

Felix Grassmann ◽

Moritz Lindner ◽

Maximilian Pfau ◽

Joanna Czauderna ◽

...

Keyword(s):

Macular Degeneration ◽

Genetic Risk ◽

Risk Profile ◽

Geographic Atrophy ◽

Age Related Macular Degeneration ◽

Age Related

Download Full-text

Association Between Perifoveal Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.19-27475 ◽

2019 ◽

Vol 60 (13) ◽

pp. 4469 ◽

Cited By ~ 3

Author(s):

Johanna M. Seddon ◽

James P. Dossett ◽

Rafael Widjajahakim ◽

Bernard Rosner

Keyword(s):

Macular Degeneration ◽

Genetic Risk ◽

Age Related Macular Degeneration ◽

Age Related

Download Full-text

Questioning Macular Pigment Measurement Methods and Genetic Risk of Age-Related Macular Degeneration

JAMA Ophthalmology ◽

10.1001/jamaophthalmol.2018.0326 ◽

2018 ◽

Vol 136 (4) ◽

pp. 453

Author(s):

Stephen Beatty ◽

Rebecca Power ◽

John Nolan

Keyword(s):

Macular Degeneration ◽

Genetic Risk ◽

Macular Pigment ◽

Measurement Methods ◽

Age Related Macular Degeneration ◽

Age Related

Download Full-text

Discovery of Novel Genetic Risk Loci for Acute Central Serous Chorioretinopathy and Genetic Pleiotropic Effect With Age-Related Macular Degeneration

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.696885 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lei Feng ◽

Si Chen ◽

Huatuo Dai ◽

Rajkumar Dorajoo ◽

Jianjun Liu ◽

...

Keyword(s):

Macular Degeneration ◽

Genetic Risk ◽

Central Serous Chorioretinopathy ◽

Clinical Manifestations ◽

Pleiotropic Effect ◽

Age Related Macular Degeneration ◽

Chromosome 15 ◽

Nucleotide Polymorphisms ◽

Risk Effects ◽

Age Related

BackgroundCentral serous chorioretinopathy (CSC) is a severe and heterogeneous chorioretinal disorder. Shared clinical manifestations between CSC and age-related macular degeneration (AMD) and the confirmation of CFH as genetic risk locus for both CSC and AMD suggest possible common pathophysiologic mechanisms between two diseases.MethodsTo advance the understanding of genetic susceptibility of CSC and further investigate genetic pleiotropy between CSC and AMD, we performed genetic association analysis of 38 AMD-associated single nucleotide polymorphisms (SNPs) in a Chinese CSC cohort, consisting of 464 patients and 548 matched healthy controls.ResultsTwelve SNPs were found to be associated with CSC at nominal significance (p < 0.05), and four SNPs on chromosomes 1, 4, and 15 showed strong associations whose evidences surpassed Bonferroni (BF)-corrected significance [rs1410996, odds ratios (OR) = 1.47, p = 2.37 × 10–5; rs1329428, OR = 1.40, p = 3.32 × 10–4; rs4698775, OR = 1.45, p = 2.20 × 10–4; and rs2043085, OR = 1.44, p = 1.91 × 10–4]. While the genetic risk effects of rs1410996 and rs1329428 (within the well-established locus CFH) are correlated (due to high LD), rs4698775 on chromosome 4 and rs2043085 on chromosome 15 are novel risk loci for CSC. Polygenetic risk score (PRS) constructed by using three independent SNPs (rs1410996, rs4698775, and rs2043085) showed highly significant association with CSC (p = 2.10 × 10–7), with the top 10% of subjects with high PRS showing 6.39 times higher risk than the bottom 10% of subjects with lowest PRS. Three SNPs were also found to be associated with clinic manifestations of CSC patients. In addition, by comparing the genetic effects (ORs) of these 38 SNPs between CSC and AMD, our study revealed significant, but complex genetic pleiotropic effect between the two diseases.ConclusionBy discovering two novel genetic risk loci and revealing significant genetic pleiotropic effect between CSC and AMD, the current study has provided novel insights into the role of genetic composition in the pathogenesis of CSC.

Download Full-text