Genetic Determinants of Age-Related Macular Degeneration in Diverse Populations From the PAGE Study

Restrepo, Nicole A.; Spencer, Kylee L.; Goodloe, Robert; Garrett, Tiana A.; Heiss, Gerardo; Bůžková, Petra; Jorgensen, Neal W.; Jensen, Richard A.; Matise, Tara C.; Hindorff, Lucia A.; Klein, Barbara E.K.; Klein, Ronald; Wong, Tien Yin; Cheng, Ching‐Yu; Cornes, Belinda K.; Tai, E. Shyong; Ritchie, Marylyn D.; Haines, Jonathan L.; Crawford, Dana C.

doi:10.1167/iovs.14-14246

Cited by 58 publications

(36 citation statements)

References 78 publications

(100 reference statements)

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“…In addition, race appears to impact the role of various genetic influences on AMD (Restrepo et al, 2014). The effect of different genetic variants on AMD among different racial or ethnic groups will be discussed later.…”

Section: Biomarkers Of Susceptibilitymentioning

confidence: 99%

Risk factors and biomarkers of age-related macular degeneration

Lambert

Elshelmani

Singh

et al. 2016

Progress in Retinal and Eye Research

282

240

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A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings.

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Section: Biomarkers Of Susceptibilitymentioning

confidence: 99%

Risk factors and biomarkers of age-related macular degeneration

Lambert

Elshelmani

Singh

et al. 2016

Progress in Retinal and Eye Research

282

240

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“…Since the allelic frequency and associations of CFH and ARMS2 polymorphisms with AMD may vary across populations, genetic analyses were further stratified by race. (33) Similarly, to assess for effect modification by HDL, HDL2, HDL3, and apoA1, analyses of the associations between visit 1 xanthophyll intake (tertiles) and AMD status were stratified by the sample medians of these lipid biomarkers. P-values <0.10 were considered statistically significant when testing for multiplicative interaction.…”

Section: Methodsmentioning

confidence: 99%

Association between Dietary Xanthophyll (Lutein and Zeaxanthin) Intake and Early Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study

Lin

Mares

LaMonte

et al. 2017

Ophthalmic Epidemiology

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Purpose To examine the association between xanthophyll intake and prevalent early age-related macular degeneration (AMD) using data from the Atherosclerosis Risk in Communities Study (n=10,295). Potential effect modification by genetic polymorphisms and biomarkers of high-density lipoprotein (HDL) metabolism was explored. Methods Xanthophyll intake was assessed at visit 1 (1987-89) using food frequency questionnaires. Prevalent early AMD was assessed at visit 3 (1993-95) via retinal photographs. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for AMD by quintiles of xanthophyll intake, adjusted for age, sex, race, field center, and pack-years of smoking. To evaluate effect modification, the association between tertiles (T) of xanthophyll intake and AMD was stratified by complement factor H (CFH) rs1061170 and age-related maculopathy susceptibility 2 (ARMS2) rs10490924 genotypes, as well as by median cutpoints of HDL biomarkers. Results Xanthophyll intake was not associated with AMD in the overall sample, Caucasians (n=8,257), or African-Americans (n=2,038). Exploratory analyses observed that the association between xanthophyll intake and AMD varied statistically significantly by CFH rs1061170 genotype (p for interaction = 0.045) among Caucasians but not African Americans. No interactions were observed between xanthophyll intake and ARMS2 rs10490924. Moreover, higher xanthophyll intake observed a decreased odds of AMD among participants with lower HDL (OR=0.79, 95% CI 0.57-1.09) but not higher HDL (p for interaction=0.048). Conclusion Xanthophyll intake was not associated with early AMD. Further studies to investigate this association by genetic susceptibility or variations in HDL metabolism are needed.

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“…The Population Architecture Using Genomics and Epidemiology (PAGE) study demonstrated that AMD risk appears to differ with respect to lipid metabolism and cholesterol-related genes in Mexican Americans, Asian Americans, African Americans, and non-Hispanic White Europeans when all types of AMD were examined [52]. In fact, in this study, none of the major risk variants for AMD e.g., HtrA serine peptidase 1 ( HTRA1)/age-related maculopathy susceptibility 2 (ARMS2) or complement factor H ( CFH ), were significant in the non-white European populations after correction for multiple testing, but this was likely due to the small sample size used in this study [52]. However, Cheng et al found a novel variant in the CETP gene as well as novel AMD lipid/cholesterol genes associated with AMD risk in East Asians [92].…”

Section: Genome-wide and Candidate Gene Association Studies Of Amdmentioning

confidence: 99%

“…While GWAS and epidemiological studies have implicated the lipid metabolism-cholesterol pathway in AMD pathophysiology, the role is unclear and at times inconsistent [52, 53]. Given the variances within and among ethnic populations with respect to AMD genetics, prevalence, and pathology, further effort needs to be focused on working out the population-specific molecular mechanisms that may influence individual patient responses to therapeutic interventions and progression of the disease.…”

Section: Genome-wide and Candidate Gene Association Studies Of Amdmentioning

confidence: 99%

Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors

2016

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Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults over 50 years old. Genetic, epidemiological, and molecular studies are beginning to unravel the intricate mechanisms underlying this complex disease, which implicate the lipid-cholesterol pathway in the pathophysiology of disease development and progression. Many of the genetic and environmental risk factors associated with AMD are also associated with other complex degenerative diseases of advanced age, including cardiovascular disease (CVD). In this review, we present epidemiological findings associating AMD with a variety of lipid pathway genes, cardiovascular phenotypes, and relevant environmental exposures. Despite a number of studies showing significant associations between AMD and these lipid/cardiovascular factors, results have been mixed and as such the relationships among these factors and AMD remain controversial. It is imperative that researchers not only tease out the various contributions of such factors to AMD development but also the connections between AMD and CVD to develop optimal precision medical care for aging adults.

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Genetic Determinants of Age-Related Macular Degeneration in Diverse Populations From the PAGE Study

Abstract: While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations.

Cited by 58 publications

References 78 publications

Risk factors and biomarkers of age-related macular degeneration

Risk factors and biomarkers of age-related macular degeneration

Association between Dietary Xanthophyll (Lutein and Zeaxanthin) Intake and Early Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study

Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors

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