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

Millen, Amy E.; Meyers, Kristin J.; Liu, Zhe; Engelman, Corinne D.; Wallace, Robert B.; LeBlanc, Erin S.; Tinker, Lesley F.; Iyengar, Sudha K.; Robinson, Jennifer G.; Sarto, Gloria E.; Mares, Julie A.

doi:10.1001/jamaophthalmol.2015.2715

Cited by 48 publications

(31 citation statements)

References 70 publications

(116 reference statements)

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“…43 Within the sample used for this analysis, and in the overall CAREDS cohort, 14 higher HLS and dietary LZ intake were each associated with lower serum C-reactive protein, a systemic marker of inflammation, and higher vitamin D, also related to inflammatory conditions. 44–46 Protective associations between serum vitamin D, which also has anti-inflammatory properties, and AMD in women with a CC Y402H genotype 47 in this sample are described in a separate manuscript. 47 …”

Section: Discussionmentioning

confidence: 92%

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Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration

Meyers¹,

Liu²,

Millen³

et al. 2015

Ophthalmology

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Purpose Healthy diets and lifestyles are thought to protect against age-related macular degeneration (AMD), but whether the benefits vary across high risk AMD genotypes is unknown. The objective is to investigate the joint effects of healthy diet and lifestyle with genetic risk on the odds for AMD. Design Healthy lifestyles scores and their interactions with AMD risk genotypes were studied in relation to the prevalence of AMD, assessed six years later. Participants Women 50–79 years of age in the Carotenoids in Age-Related Eye Disease Study (CAREDS) with exposure and AMD data available (N=1,663). Methods Healthy lifestyle scores (0–6 points) were assigned based on Healthy Eating Index scores, physical activity (MetHrs/week), and pack years of smoking assessed between 1994–1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Interactions between healthy lifestyle score and genotype in relation to the odds of AMD were assessed. Main Outcome Stereoscopic fundus photographs were taken and graded for AMD six years after exposure assessment (2001–2004). A total of 308 women had early AMD and 29 had late AMD). Results The odds of AMD were 3.3 times greater in women with both low healthy lifestyle score (0–2) and high risk CFH genotype (CC), relative to those who had low genetic risk (TT) and healthy lifestyle scores of 4–6 (95% CI:1.8–6.1). There were no significant additive (SI=1.08, 95% CI: 0.70–1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. Limiting the sample to those with stable diets prior to AMD assessment (n=728) strengthened the joint effects (OR=4.6, 95% CI: 1.85–11.6) and suggested high risk genotype and low lifestyle score combined had a stronger association than expected by simply adding the two effects (SI=1.34, 95% CI: 1.05–1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained the joint association. There was no significant evidence of additive or multiplicative interactions for ARMS2 and lifestyle score. Conclusions These results, in a sample in which the majority of AMD cases were early, suggest the effects of high risk Y402H genotype and poor diets and lifestyles combine in at least an additive manner to influence odds for AMD, but may combine to be more than the sum of their individual effects.

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Section: Discussionmentioning

confidence: 92%

“…44–46 Protective associations between serum vitamin D, which also has anti-inflammatory properties, and AMD in women with a CC Y402H genotype 47 in this sample are described in a separate manuscript. 47 …”

Section: Discussionmentioning

confidence: 92%

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration

Meyers¹,

Liu²,

Millen³

et al. 2015

Ophthalmology

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“…Both scores of bone-mineral density (in the femoral neck and in the lumbar spine) are nominally significant, suggesting a protective effect for AMD in individuals having a higher bone-mineral density. Interestingly, vitamin D deficiency was linked to incident AMD in the CARED study [115] and bone-mineral density can be increased with vitamin D supplementation [116]. Of note, neither the genetic score of serum calcium concentration nor vitamin D concentration was found to be significantly associated with AMD.…”

Section: Discussionmentioning

confidence: 99%

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

et al. 2017

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BackgroundAge-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits.MethodsFor each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression.ResultsOf the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27–20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 × 10–16 to 1.9 × 10–3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 × 10–7 to 3.0 × 10–4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis.ConclusionsWe demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0418-0) contains supplementary material, which is available to authorized users.

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“…2015 124 observed a 6.7-fold increased risk of age-related macular degeneration (AMD) among women with serum 25(OH)D levels less than 12 ng/mL who also had genetic risk for AMD, and noted that previous studies had found that decreased odds of AMD are associated with high compared to low concentrations of 25(OH)D.…”

Section: Macular Degenerationmentioning

confidence: 99%

The risks and benefits of sun exposure 2016

Hoel

Berwick

Gruijl

et al. 2016

Dermato-Endocrinology

107

102

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Public health authorities in the United States are recommending that men, women and children reduce their exposure to sunlight, based on concerns that this exposure will promote skin cancer. On the other hand, data show that increasing numbers of Americans suffer from vitamin D deficiencies and serious health problems caused by insufficient sun exposure. The body of science concerning the benefits of moderate sun exposure is growing rapidly, and is causing a different perception of sun/UV as it relates to human health. Melanoma and its relationship to sun exposure and sunburn is not adequately addressed in most of the scientific literature. Reports of favorable health outcomes related to adequate serum 25(OH)D concentration or vitamin D supplementation have been inappropriately merged, so that benefits of sun exposure other than production of vitamin D are not adequately described. This review of recent studies and their analyses consider the risks and benefits of sun exposure which indicate that insufficient sun exposure is an emerging public health problem. This review considers the studies that have shown a wide range health benefits from sun/UV exposure. These benefits include among others various types of cancer, cardiovascular disease, Alzheimer disease/dementia, myopia and macular degeneration, diabetes and multiple sclerosis. The message of sun avoidance must be changed to acceptance of non-burning sun exposure sufficient to achieve serum 25(OH)D concentration of 30 ng/mL or higher in the sunny season and the general benefits of UV exposure beyond those of vitamin D.

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

Cited by 48 publications

References 70 publications

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

The risks and benefits of sun exposure 2016

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