scholarly journals Casual Effect of Serum Lipid Biomarkers On Early Age-Related Macular Degeneration Using Mendelian Randomization

2021 ◽  
Author(s):  
Fen-Fen Li ◽  
Yuqin Wang ◽  
Qi Chen ◽  
Lue Xiang ◽  
Feng-Qin Rao ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipid Biomarkers ◽  
Age Related Macular Degeneration ◽  
Lipoprotein Cholesterol ◽  
European Ancestry ◽  
Age Related ◽  
Increased Risk

Abstract Background Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, whereas lipid biomarkers’ casual effects on early AMD remain unclear. Methods In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers, consisting of apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG), and the risk of early AMD. Totally, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (Number of SNPs = 11,304,110). Results MR estimates showed that a higher HDL-C level was strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10−8). In addition, the level of ApoA was also positively associated with the risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10−6). Conversely, higher LDL-C levels significantly decreased the risk of early AMD (OR = 0.90, 95% CI: 0.85-0.96, P = 2.03 × 10−3). In addition to LDL-C, higher levels of ApoB and TG were found to be positively associated with early AMD risk. Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. Conclusion This study addresses the question of causality relationships that elevated circulating HDL-C/ApoA levels and increased risk of early AMD, whereas LDL-C, ApoB, and TG specifically reduce the risk of early AMD. These findings contribute to our better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study

2020 ◽  
Author(s):  
Xikun Han ◽  
Jue-Sheng Ong ◽  
Alex W Hewitt ◽  
Puya Gharahkhani ◽  
Stuart MacGregor
Keyword(s):  
Macular Degeneration ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipid Biomarkers ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
European Descent ◽  
Age Related

Abstract Background Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear. Methods Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64–407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium. Results Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. Conclusion These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD.

Effect of intravitreal injection of aflibercept on cardiovascular risk parameters in patients with neovascular age related macular degeneration

2020 ◽  
Vol 15 ◽  
Author(s):  
Constantinos D. Georgakopoulos ◽  
Athina Pallikari ◽  
Panagiotis Plotas ◽  
Konstantinos Kagkelaris ◽  
Stylianos Mastronikolis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Macular Degeneration ◽  
Intravitreal Injection ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Age Related Macular Degeneration ◽  
Lipoprotein Cholesterol ◽  
Age Related ◽  
Increased Risk ◽  
Oncologic Patients

Objective: Systemic administration of anti-vascular endothelial growth factors (anti-VEGFs) has been associated with severe cardiovascular adverse events in oncologic patients. The purpose of this pilot study is to evaluate the short-term effect of a single intravitreal injection of aflibercept on biomarkers related to increased risk of cardiovascular disease. Patients and Methods: Forty-seven treatment naïve patients with neovascular age related macular degeneration in one eye were enrolled in the study. The patients underwent treatment with one intravitreal injection of aflibercept in the affected eye. Laboratory biomarkers of cardiovascular disease were evaluated before the first intravitreal injection of aflibercept and at 7 and 30 days after aflibercept administration. More precisely, we evaluated the levels of homocysteine, total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol and C-reactive protein. Results: There was not any statistically significant change in the levels of the evaluated parameters up to one month after the first intravitreal injection of aflibercept. Conclusions: According to our study, administration of a single dose of aflibercept in eyes with neovascular age-related macular degeneration does not seem to affect the evaluated biomarkers that are related to cardiovascular disease.

Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: two population cohorts

2021 ◽  
Author(s):  
Liv Tybjærg Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Ruth Frikke-Schmidt ◽  
Børge Grønne Nordestgaard
Keyword(s):  
Macular Degeneration ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Age Related ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Plasma Apolipoprotein

Abstract Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.

scholarly journals Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration

2015 ◽  
Author(s):  
Erin K. Wagner ◽  
Yi Yu ◽  
Eric H. Souied ◽  
Sanna Seitsonen ◽  
Ilkka J. Immonen ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Rare Variants ◽  
Association Studies ◽  
Low Frequency ◽  
Density Lipoprotein ◽  
Age Related Macular Degeneration ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Meta Analyses

ABSTRACTAlthough >20 common frequency age-related macular degeneration (AMD) alleles have been discovered with genome-wide association studies, substantial disease heritability remains unexplained. In this study we sought to identify additional variants, both common and rare, that have an association with advanced AMD. We genotyped 4,332 cases and 25,268 controls of European ancestry from three different populations using the Illumina Infinium HumanExome BeadChip. We performed meta-analyses to identify associations with common variants and performed single variant and gene-based burden tests to identify associations with rare variants. Two protective, low frequency, non-synonymous variants A307V in PELI3 (odds ratio [OR]=0.14, P=4.3×10−10) and N1050Y in CFH (OR=0.76, Pconditional=1.6×10−11) were significantly associated with a decrease in risk of AMD. Additionally, we identified an enrichment of protective alleles in PELI3 using a burden test (OR=0.14). The new variants have a large effect size, similar to rare mutations we reported previously in a targeted sequencing study, which remain significant in this analysis: CFH R1210C (OR=18.82, P=3.5×10−07), C3 K155Q (OR=3.27, P=1.5×10−10), and C9 P167S (OR=2.04, P=2.8×10−07). We also identified a strong protective signal for a common variant (rs8056814) near CTRB1 associated with a decrease in AMD risk (logistic regression: OR = 0.71, P = 1.8x10−07; Firth corrected OR = 0.64, P = 9.6x10−11). This study supports the involvement of both common and low frequency protective variants in AMD. It also may expand the role of the high-density lipoprotein pathway and branches of the innate immune pathway, outside that of the complement system, in the etiology of AMD.

scholarly journals Study of association between the serum lipid profile and age-related macular degeneration in a tertiary care centre of Central UP

2019 ◽  
Vol 7 (4) ◽  
pp. 1104 ◽  
Author(s):  
Ahmad Husain ◽  
Brijesh Singh ◽  
Ravi Ranjan ◽  
Kalbe Jawad ◽  
Ifsa Sami ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Lipid Profile ◽  
Serum Lipid ◽  
Tertiary Care ◽  
Positive Association ◽  
Age Related Macular Degeneration ◽  
Tertiary Care Centre ◽  
Age Related ◽  
Increased Risk ◽  
The Relationship

Background: Age-related macular degeneration (ARMD) is the major challenge in the new millennium in the developing countries as the size of elderly population continues to rise due to betterment of medical facilities and increased life expectancy. Lipids are implicated in the pathogenesis of ARMD. The relationship between systemic lipids and ARMD has not been well characterized, especially in rural population. The objective was to investigate the relationship between serum lipids and ARMD in older adults.Methods: In this case-control study, 300 adults, aged ≥50 years, 150 each among cases and controls were included in the study. Mean lipids values between cases and controls were compared.Results: Mean age of cases was 62.45±8.472 years and mean age of controls was 61.89±8.51 years. Among 150 cases, 124 (82.66%) cases were of dry ARMD while 26 (17.33%) cases were Wet ARMD. Author found that 38 cases among total cases (25.33%) and 15 individuals (10%) among controls had altered lipid profile. All mean lipid values were higher among cases compare to controls (p>0.05), while the mean of VLDL, TG and TG/HDL were significantly raised showing positive association (p<0.05).Conclusions: Present study showed that high levels of serum lipid values especially VLDL, TG and TG/HDL positive association with an increased risk for development of ARMD, implying that strategies reducing serum lipid levels may be useful to prevent the development of the disease.

scholarly journals Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shu-Yi Huang ◽  
Yu-Xiang Yang ◽  
Shi-Dong Chen ◽  
Hong-Qi Li ◽  
Xue-Qing Zhang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Body Fat ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Environmental Exposures ◽  
Lipoprotein Cholesterol ◽  
European Ancestry ◽  
Human Longevity ◽  
Lower Odds ◽  
Age Related

Abstract Background Environmental factors are associated with human longevity, but their specificity and causality remain mostly unclear. By integrating the innovative “exposome” concept developed in the field of environmental epidemiology, this study aims to determine the components of exposome causally linked to longevity using Mendelian randomization (MR) approach. Methods A total of 4587 environmental exposures extracting from 361,194 individuals from the UK biobank, in exogenous and endogenous domains of exposome were assessed. We examined the relationship between each environmental factor and two longevity outcomes (i.e., surviving to the 90th or 99th percentile age) from various cohorts of European ancestry. Significant results after false discovery rates correction underwent validation using an independent exposure dataset. Results Out of all the environmental exposures, eight age-related diseases and pathological conditions were causally associated with lower odds of longevity, including coronary atherosclerosis (odds ratio = 0.77, 95% confidence interval [0.70, 0.84], P = 4.2 × 10−8), ischemic heart disease (0.66, [0.51, 0.87], P = 0.0029), angina (0.73, [0.65, 0.83], P = 5.4 × 10−7), Alzheimer’s disease (0.80, [0.72, 0.89], P = 3.0 × 10−5), hypertension (0.70, [0.64, 0.77], P = 4.5 × 10−14), type 2 diabetes (0.88 [0.80, 0.96], P = 0.004), high cholesterol (0.81, [0.72, 0.91], P = 0.0003), and venous thromboembolism (0.92, [0.87, 0.97], P = 0.0028). After adjusting for genetic correlation between different types of blood lipids, higher levels of low-density lipoprotein cholesterol (0.72 [0.64, 0.80], P = 2.3 × 10−9) was associated with lower odds of longevity, while high-density lipoprotein cholesterol (1.36 [1.13, 1.62], P = 0.001) showed the opposite. Genetically predicted sitting/standing height was unrelated to longevity, while higher comparative height size at 10 was negatively associated with longevity. Greater body fat, especially the trunk fat mass, and never eat sugar or foods/drinks containing sugar were adversely associated with longevity, while education attainment showed the opposite. Conclusions The present study supports that some age-related diseases as well as education are causally related to longevity and highlights several new targets for achieving longevity, including management of venous thromboembolism, appropriate intake of sugar, and control of body fat. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations.

scholarly journals Bidirectional Mendelian randomization analysis of shared genetic signals between coexisting neurodegenerative disorders to decipher underlying causal pathways

2019 ◽  
Author(s):  
Sandeep Grover ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Macular Degeneration ◽  
Neurodegenerative Disorders ◽  
Mendelian Randomization ◽  
Age Related Macular Degeneration ◽  
European Ancestry ◽  
Age Related

ABSTRACTOBJECTIVETo investigate whether coexistence of various neurodegenerative disorders is coincidental or biologically connected.DESIGNTwo sample Mendelian randomization using summary effect estimatesSETTINGGenetic data taken on various neurodegenerative disorders from various cohorts comprising individuals predominantly of European ancestry.PARTICIPANTSInternational Genomics of Alzheimer’s patients (IGAP), project MinE, International Age-related Macular Degeneration Consortium (IAMDGC), International Multiple Sclerosis Genetics Consortium (IMSGC), International Parkinson’s Disease Genomics Consortium (IPDGC)MAIN OUTCOME MEASURESAlzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Age related macular degeneration (AMD), Multiple sclerosis (MS) and Parkinson’s disease (PD).RESULTSA Bonferroni corrected threshold of P=0.005 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. I observed a risky effect of PD on ALS (OR = 1.126, 95% CI = 1.059-1.198, P = 0.005). Using AD as exposure and PD as outcome, I observed a risky effect of AD on PD using all the MR methods with strongest results using MBE method (OR = 2.072, 95% CI = 1.006-4.028, P = 0.0416). Genetic predisposition to AD was further observed to be a risky for AMD (OR = 1.759, 95% CI = 1.040-1.974, P = 0.0363). On the contrary, AMD was observed to be strongly protective towards MS (OR = 0.861, 95% CI = 0.776-0.955, P = 0.0059).CONCLUSIONSMy findings are consistent with the previously observed relative occurrence of co-existing neurodegenerative diseases or overlapping symptoms among neurodegenerative diseases.

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