scholarly journals Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration

2020 ◽  
Vol 13 (9) ◽  
pp. 257 ◽  
Author(s):  
Taiyo Shijo ◽  
Yoichi Sakurada ◽  
Seigo Yoneyama ◽  
Wataru Kikushima ◽  
Atsushi Sugiyama ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Risk Score ◽  
Positive Association ◽  
Age Related Macular Degeneration ◽  
P Value ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Risk Variants ◽  
Age Related ◽  
One Year

We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (n = 129) and polypoidal choroidal vasculopathy (n = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), SKIV2L-C2-CFB (rs429608), C3 (rs2241394), ADAMTS-9 (rs6795735) and CETP (rs3764261) was performed for all participants. A total of 63 PRSs were quantified. There was a positive association between the PRS involving ARMS2, CFH, C3, and ADAMTS-9 and best-corrected visual acuity at twelve months (p = 0.046, multiple regression analysis). When comparing PRSs of patients requiring retreatment and of patients without retreatment, 35 PRSs were significantly greater in patients requiring retreatment than in patients without requiring retreatment, with the PRS involving ARMS2 and CFH being most significantly associated (p = 1.6 × 10−4). The number of additional injections was significantly associated with 40 PRSs and the PRS involving ARMS2 and CFH showed a most significant p-value (p = 2.42 × 10−6). Constructing a PRS using a combination with high-risk variants might be informative for predicting the response to IAI for exudative AMD.

scholarly journals Photoreceptor layer thinning is an early biomarker for age-related macular degeneration development: Epidemiological and genetic evidence from UK Biobank optical coherence tomography data

2021 ◽  
Author(s):  
Seyedeh Maryam Zekavat ◽  
Sayuri Sekimitsu ◽  
Yixuan Ye ◽  
Hongyu Zhao ◽  
Tobias Elze ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Early Stage ◽  
Age Related Macular Degeneration ◽  
Retinal Layer ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Age Related ◽  
Clinical Biomarker

AbstractIntroductionAge-related macular degeneration (AMD) is a blinding condition for which there is currently no early-stage clinical biomarker. AMD is characterized by thinning of the outer retina and drusen formation leading to thickening of the Bruch’s membrane and RPE complex, but the timing between these two events, as well as the role of genetic variants in these processes, are unclear. Here, we jointly analyzed genomic, electronic health record, and optical coherence tomography (OCT) data across 44,823 individuals from the UK Biobank to characterize the epidemiological and genetic associations between retinal layer thicknesses and AMD.MethodsThe Topcon Advanced Boundary Segmentation algorithm was used for automated retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model, and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we tested the association of AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age2, sex, smoking status, and principal components of ancestry.ResultsPhotoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed and accelerated at age 45, while retinal pigment epithelium and Bruch’s membrane complex (RPE+BM) thickening started after age 57. Each standard deviation (SD) of PS thinning and RPE+BM thickening were associated with prevalent AMD (PS: OR 1.37, 95% CI 1.25-1.49, P=2.5×10−12; RPE+BM: OR=1.34, 95% CI 1.27-1.41, P=8.4×10−28) and incident AMD (PS: HR 1.35, 95% CI 1.23-1.47, P=3.7×10−11; RPE+BM: HR 1.14, 95% CI 1.06-1.22, P=0.00024). An AMD polygenic risk score (PRS) was associated with PS thinning (Beta -0.21 SD per 2-fold genetically increased risk of AMD, 95% CI -0.23 to -0.19, P=2.8×10−74), and its association with RPE+BM was U-shaped (thinning with AMD PRS<92nd percentile and thickening with AMD PRS>92nd percentile suggestive of drusen formation). The loci with strongest support were AMD risk-raising variants CFH:rs570618-T, CFH:10922109-C, and ARMS2/HTRA1:rs3750846-C on PS thinning, and SYN3/TIMP3:rs5754227-T on RPE+BM thickening.ConclusionsEpidemiologically, PS thinning precedes RPE+BM thickening by decades, and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage clinical biomarker for future AMD development.

scholarly journals A Risk Score for the Prediction of Advanced Age-Related Macular Degeneration

Ophthalmology ◽  
2014 ◽  
Vol 121 (7) ◽  
pp. 1421-1427 ◽  
Author(s):  
Chung-Jung Chiu ◽  
Paul Mitchell ◽  
Ronald Klein ◽  
Barbara E. Klein ◽  
Min-Lee Chang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Risk Score ◽  
Age Related Macular Degeneration ◽  
Advanced Age ◽  
Age Related

scholarly journals Polygenic risk for schizophrenia, transition and cortical gyrification: a high-risk study

2017 ◽  
Vol 48 (9) ◽  
pp. 1532-1539 ◽  
Author(s):  
E. Neilson ◽  
C. Bois ◽  
T.-K. Clarke ◽  
L. Hall ◽  
E. C. Johnstone ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Familial Risk ◽  
Positive Association ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Score Analysis ◽  
Increased Risk ◽  
Heritable Disorder ◽  
Diagnostic Symptoms

AbstractBackgroundSchizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.MethodsThe current study included participants at high familial risk of schizophrenia who remained well (n= 31), who developed sub-diagnostic symptoms (n= 28) and who developed schizophrenia (n= 9) as well as healthy controls (HC) (n= 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.ResultsWe found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.ConclusionsThese results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.

scholarly journals Effect of Ranibizumab Treatment in Cases of Choroidal Neovascular Membranes Secondary to Pathological Myopia versus Age-Related Macular Degeneration

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M S Abdaltawab ◽  
Z F Ismail ◽  
W M A Ebeid ◽  
S M Fawzy
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
P Value ◽  
Newly Diagnosed ◽  
Pathological Myopia ◽  
Age Related ◽  
Significant Difference ◽  
The Mean

Abstract Aim of the Work The aim of this work is to compare the response of treatment with ranibizumab in terms of visual acuity in cases of CNV secondary to pathological myopia versus CNV secondary to age-related macular degeneration. Methods This prospective, comparative study included ten eyes newly diagnosed as having CNV secondary to pathological myopia, and 10 eyes newly diagnosed as having subfoveal active CNV secondary to AMD. All patients had 3 monthly intravitreal Injections of 0.50 mg (in 0.05 ml of solution) ranibizumab with monthly evaluation of best corrected visual acuity (BCVA) by Landolt C chart, and also calculated in Logarithm of Minimum Angle of Resolution (Log MAR). Results pretreatment there was no significant difference between the two groups as the mean VA (Log Mar) was 1.31 ± 0.2 in AMD group and 1.17 ± 0.3 in MCNV group of P value = 0.431 and also post three IVI of ranibizumab showed no significant difference between the two groups as the mean VA (Log Mar) was 1.22 ± 0.2 for AMD and 1.22 ± 0.5 for MCNV of P value = 0.635. Conclusion there was no significant difference in BCVA between AMD and MCNV groups after three intravitreal injections of ranibizumab.

Intravitreal Bevacizumab for Treatment of Neovascular Age-related Macular Degeneration: A One-year Prospective Study

2008 ◽  
Vol 145 (2) ◽  
pp. 249-256.e2 ◽  
Author(s):  
Ziad F. Bashshur ◽  
Zeina A. Haddad ◽  
Alexandre Schakal ◽  
Rola F. Jaafar ◽  
Marc Saab ◽  
...  
Keyword(s):  
Prospective Study ◽  
Macular Degeneration ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
One Year

scholarly journals Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Clara Bodelon ◽  
Hannah Oh ◽  
Andriy Derkach ◽  
Joshua N. Sampson ◽  
Brian L. Sprague ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Intermediate Step ◽  
Breast Cancers ◽  
Tissue Samples ◽  
Polygenic Risk ◽  
Age Related

Abstract Terminal duct lobular units (TDLUs) are the predominant anatomical structures where breast cancers originate. Having lesser degrees of age-related TDLU involution, measured as higher TDLUs counts or more epithelial TDLU substructures (acini), is related to increased breast cancer risk among women with benign breast disease (BBD). We evaluated whether a recently developed polygenic risk score (PRS) based on 313-common variants for breast cancer prediction is related to TDLU involution in the background, normal breast tissue, as this could provide mechanistic clues on the genetic predisposition to breast cancer. Among 1398 women without breast cancer, higher values of the PRS were significantly associated with higher TDLU counts (P = 0.004), but not with acini counts (P = 0.808), in histologically normal tissue samples from donors and diagnostic BBD biopsies. Mediation analysis indicated that TDLU counts may explain a modest proportion (≤10%) of the association of the 313-variant PRS with breast cancer risk. These findings suggest that TDLU involution might be an intermediate step in the association between common genetic variation and breast cancer risk.

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