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2.
Nat Commun ; 10(1): 4130, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511532

RESUMO

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

3.
Br J Ophthalmol ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558494

RESUMO

BACKGROUND: To examine the normative profile and determinants of retinal nerve fibre layer (RNFL) symmetry in a non-glaucoma, multiethnic Asian population. METHODS: Chinese, Malay and Indian adults aged ≥40 years were recruited from the Singapore Epidemiology of Eye Diseases study. Participants underwent standardised systemic and ocular examinations. RNFL thickness was obtained using a spectral-domain optical coherence tomography (Cirrus HD-OCT). RNFL symmetry (in %) was calculated based on Pearson correlation coefficient between the RNFL thickness profiles of the right and left eyes. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with RNFL symmetry. RESULTS: 4211 participants (1227 Chinese, 1245 Malays, 1739 Indians) were included. The mean RNFL symmetry was 86.7%±8.5% in Chinese, 84.7%±10.2% in Malays and 84.0%±10.7% in Indians. The fifth percentile limit of RNFL symmetry was 71.2% in Chinese, 65.0% in Malays and 62.0% in Indians. In multivariable analysis adjusting for age, gender, ethnicity, hypertension, diabetes, hyperlipidaemia, intereye absolute differences in intraocular pressure (IOP), axial length and disc area, Malays (ß=-0.9; p=0.03) and Indians (ß=-1.76; p<0.001) were found to have lower RNFL symmetry compared with Chinese. Older age, greater intereye differences in IOP, axial length and disc area were significantly associated with lower RNFL symmetry (all p≤0.003). CONCLUSIONS: In non-glaucoma individuals, intereye RNFL profile is less symmetric in Malays and Indians than that in Chinese. This also suggests that current commercial optical coherence tomography's deployment of a single, universal RNFL symmetry cut-off for glaucoma detection is flawed, and ethnic-specific cut-off is warranted.

4.
Br J Ophthalmol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492674

RESUMO

BACKGROUND/AIMS: Although being a more objective tool for assessment and follow-up of angle closure, reliability studies have reported a moderate diagnostic performance for anterior segment optical coherence tomography (OCT) technologies when comparing with gonioscopy as the reference standard. We aim to determine factors associated with diagnostic disagreement in angle closure when assessed by anterior segment swept source OCT (SS-OCT, CASIA SS-1000; Tomey, Nagoya, Japan) and gonioscopy. METHODS: Cross-sectional study. A total of 2027 phakic subjects aged ≥50 years, with no relevant previous ophthalmic history, were consecutively recruited from a community polyclinic in Singapore. Gonioscopy and SS-OCT (128 radial scans) for the entire circumference of the angle were performed for each subject. A two-quadrant closed gonioscopic definition was used. On SS-OCT images, angle closure was defined as iridotrabecular contact (ITC) to the extent of ≥35%, ≥50% and ≥75% of the circumferential angle. Diagnostic disagreements between both methods, that is, false positives or overcalls and false negatives or undercalls were defined, respectively, as gonioscopic open/closed angles inversely assessed as closed/open by SS-OCT. RESULTS: Two hundred and seventy-two (14.7%) resulted in overcall results (false positives) when ≥50% of the angle circumference was closed using SS-OCT. These eyes had significantly wider (anterior chamber width, 11.7 vs 11.6 mm, p<0.001) and deeper (anterior chamber depth (ACD), 2.4 vs 2.2 mm, p<0.001) anterior chambers than eyes assessed by both methods as closed (true positives). Deeper ACD (OR 9.31) and lower lens vault (LV) (OR 0.04) were significantly associated with a false positive diagnosis in the multivariate analysis. Most of these cases had short (52.6%) or irregular (39%) ITC in SS-OCT images. CONCLUSIONS: We found that anterior chamber dimensions, determined by ACD and LV, were factors significantly associated with diagnostic disagreement between anterior segment SS-OCT and gonioscopy in angle closure assessment.

5.
J Rheumatol ; 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31523044

RESUMO

OBJECTIVE: We aimed to present a systematic evaluation of 47 non Major Histocompatibility Complex (MHC) Ankylosing Spondylitis (AS) susceptibility loci which have been initially discovered through Caucasian Genome-wide association studies (GWASs) in Han Chinese. METHODS: Totally 10,743 samples representing north and south Chinese in four datasets were obtained. After data quality control and imputation, meta-analysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages (PARPs) of AS-associated variants were compared. Functional annotation of AS-associated variants were conducted using HaploReg, RegulomeDB and rVarBase Database. RESULTS: We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (P=6.30×10-10), rs10050860 (P=4.09×10-5) and rs8070463 (P=1.03×10-4). Potential susceptible SNPs within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15) and rs62074054 (17q21). Epistatic ineractions between three ERAP1 SNPs (rs17401719, rs30187 and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than Caucasians. Further genomic annotation pinpointed 35 candidate functional SNPs, especially in 2p15, ERAP1 and NPEPPS-TBKBP1 region. CONCLUSION: Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1 and NPEPPS-TBKBP1 region may play a critical role in AS pathogenesis across diverse populations.

6.
Br J Ophthalmol ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462416

RESUMO

BACKGROUND: To determine the prevalence and causes of blindness and vision impairment (VI) in East Asia in 2015 and to forecast the trend to 2020. METHODS: Through a systematic literature review and meta-analysis, we estimated prevalence of blindness (presenting visual acuity <3/60 in the better eye), moderate-to-severe vision impairment (MSVI; 3/60≤presenting visual acuity <6/18), mild vision impairment (mild VI: 6/18≤presenting visual acuity <6/12) and uncorrected presbyopia for 1990, 2010, 2015 and 2020. A total of 44 population-based studies were included. RESULTS: In 2015, age-standardised prevalence of blindness, MSVI, mild VI and uncorrected presbyopia was 0.37% (80% uncertainty interval (UI) 0.12%-0.68%), 3.06% (80% UI 1.35%-5.16%) and 2.65% (80% UI 0.92%-4.91%), 32.91% (80% UI 18.72%-48.47%), respectively, in East Asia. Cataract was the leading cause of blindness (43.6%), followed by uncorrected refractive error (12.9%), glaucoma, age-related macular degeneration, corneal diseases, trachoma and diabetic retinopathy (DR). The leading cause for MSVI was uncorrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, corneal disease, trachoma and DR. The burden of VI due to uncorrected refractive error, cataracts, glaucoma and DR has continued to rise over the decades reported. CONCLUSIONS: Addressing the public healthcare barriers for cataract and uncorrected refractive error can help eliminate almost 57% of all blindness cases in this region. Therefore, public healthcare efforts should be focused on effective screening and effective patient education, with access to high-quality healthcare.

7.
Invest Ophthalmol Vis Sci ; 60(10): 3275-3282, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369672

RESUMO

Purpose: To define the shape of the anterior surface of the peripapillary sclera (PPS) and evaluate its relationship with age and ocular determinants in a population-based Chinese cohort. Methods: The optic nerve heads of 619 healthy Chinese subjects were imaged with spectral-domain optical coherence tomography. To assess the shape of the PPS/Bruch's membrane (BM), we measured the angle between a line parallel to the nasal anterior PPS/BM boundary and one parallel to the temporal side. A negative value indicated that the PPS/BM followed an inverted v-shaped configuration (peak pointing toward the vitreous), whereas a positive value indicated that it followed a v-shaped configuration (peak pointing toward the orbital tissues). A linear regression model was used to evaluate the relationship between the PPS angle and other ocular parameters. Results: The mean PPS angle was 3.68° ± 6.73° and the BM angle was 9.69° ± 5.05°. The PPS angle increased on average by 0.233 deg/y. A v-shaped PPS was significantly associated with age (ß = 0.087, P = 0.004), peripapillary choroidal thickness (ß = -0.479, P < 0.001), lamina cribrosa depth (ß = 0.307, P < 0.001), and BM angle (ß = 0.487, P < 0.001) after adjusting for best corrected visual acuity, central corneal thickness, and axial length. Conclusions: The anterior surface of PPS of an elderly adult population had a v-shaped configuration and was more pronounced with increasing age, thin peripapillary choroid, and a deep cup. Such a change in shape with age could have an impact on the biomechanical environment of the optic nerve head.

8.
Am J Ophthalmol ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377279

RESUMO

PURPOSE: The purpose of this study was to investigate whether the addition of primary angle closure glaucoma (PACG) associated genetic loci allows improved detection of PACG, compared to anterior segment parameters measured by imaging. DESIGN: Case-control study METHODS: Genotype data of the 8 PACG SNPs (rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on Chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were available. Customized software was used to measure anterior segment optical coherence tomography (ASOCT) parameters, namely anterior chamber depth, width, and area (ACD, ACW, ACA) and lens vault (LV). Statistical analysis for positive predictive values was modelled using the Receiver operating characteristic curve (AUC). Statistical significance comparing predictive power of the different parameters was calculated using permutation. RESULTS: A total of 388 PACG subjects and 751 controls with both ASOCT and genetic data were available for analysis. Anterior segment parameters including ACD, ACA, and LV had excellent predictive value (AUC) >0.94), except ACW (AUC=0.65) for identifying PACG. The inclusion of genetic risk alleles (either singly or as a composite genetic risk score for 8 GWAS SNPs) to ACD only provided a +0.50% improvement in re-classifying PACG cases and controls over and above the discriminatory value of ACD. This +0.50% improvement was not statistically significant (P>0.05). CONCLUSIONS: Although significant on their own, the incorporation of genetic data in the context of anterior segment imaging parameters like ACD provided only a marginal improvement of PACG detection.

9.
Br J Ophthalmol ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401553

RESUMO

BACKGROUND/AIMS: In order to address the eye care needs of the increasing numbers of elderly Chinese globally, there is a need for comprehensive understanding on the longitudinal trends of age-related eye diseases among Chinese. We herein report the key findings from the baseline Singapore Chinese Eye Study (SCES-1), and describe the rationale and methodology of the 6-year follow-up study (SCES-2). METHODS: 3353 Chinese adults who participated in the baseline SCES-1 (2009-2011) were invited for the 6-year follow-up SCES-2 (2015-2017). Examination procedures for SCES-2 included standardised ocular, systemic examinations and questionnaires identical to SCES-1. SCES-2 further included new examinations such as optical coherence tomography angiography, and questionnaires to evaluate health impact and economic burden of eye diseases. RESULTS: In SCES-1, the age-adjusted prevalence of best-corrected low vision (VA<6/12, better-seeing eye) and blindness (VA<6/60, better-seeing eye) were 3.4% and 0.2%, respectively. The prevalence rates for glaucoma, age related macular degeneration, and diabetic retinopathy (among diabetics) were 3.2%, 6.8%, 26.2%, respectively. Of the 3033 eligible individuals from SCES-1, 2661 participated in SCES-2 (response rate=87.7%). Comparing with those who did not attend SCES-2, those attended were younger, had higher SES (all p<0.001), but less likely to be a current smoker, to have diabetes, hypertension, hyperlipidaemia (all p≤0.025). CONCLUSIONS: Building on SCES-1, SCES-2 will be one of the few longitudinal population-based eye studies to report incidence, progression, and risk factors of major age-related eye diseases. Findings from this cohort may offer new insights, and provide useful reference information for other Chinese populations elsewhere.

10.
PLoS One ; 14(8): e0220143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415580

RESUMO

PURPOSE: To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM). METHODS: A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM). RESULTS: In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance. CONCLUSIONS: Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.

11.
J Alzheimers Dis ; 71(1): 341-351, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381520

RESUMO

BACKGROUND: Dementia is the leading cause of dependency and disability among older persons worldwide. There remains, however, limited studies on dementia rates within the Asia-Pacific region, with little data on differences across major Asian ethnic groups. OBJECTIVE: To study the prevalence of cognitive impairment (CI) and dementia in community-dwelling Indians from Singapore and to examine interethnic differences among Chinese, Malays, and Indians. METHODS: Participants (>60 years) drawn from the Indian component of the multiethnic Epidemiology of Dementia in Singapore (EDIS) study were screened using the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen-positive participants underwent further detailed neuropsychological assessments. CI was classified into Cognitive impairment no dementia (CIND)-mild, CIND-moderate, and dementia. RESULTS: Of 961 Indian adults, 120 (12.5%) had CIND-mild, 101 (10.5%) CIND-moderate, and 12 (1.2%) dementia. The overall age-standardized prevalence of any CI was 24.6%. The prevalence of any CI increased with age (15.7% in ages 60-64 years to 30.1% in ages≥80 years), and was higher in women than men. Multivariate analysis showed that age, lower education, and hypertension were independently associated with CI. Even after demographic and cardiovascular risk factor adjustment, Indians were more likely to be cognitively impaired compared to Chinese (odds ratio [OR], 95% CI:1.37 [1.01-1.86]) but not Malays (0.89 [0.72-1.10]). CONCLUSIONS: Among elderly Indians, the overall prevalence of any CI was 24.6%. Despite similar assessment protocols and risk factor adjustments, the prevalence of CI was higher in Indians compared to Chinese but similar to Malays. Further research is needed to unravel other factors that may underlie these ethnic differences.

12.
Br J Ophthalmol ; 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272959

RESUMO

BACKGROUND/AIMS: To evaluate the association between systemic medications and cortical cataract prevalence in an Asian population. METHODS: The Singapore Epidemiology of Eye Diseases Study recruited 10 033 Chinese, Malay and Indian residents aged 40+ years living in Singapore. Information on medication use was collected at interview using questionnaires. The presence and severity of cortical cataract were assessed from lens photographs using the modified Wisconsin Cataract Grading System. Associations between medications and the presence of cortical cataract were assessed using logistic regression. Associations between medications and greater severity of cortical cataract (none, minimal, early and late) were assessed using ordinal logistic regression. RESULTS: A total of 8965 participants were included, the mean age was 57.6 (SD=9.8) years, and 4555 (50.8%) were women. After adjusting for age, gender, ethnicity, body mass index, smoking status, socioeconomic status, hypertension, hyperlipidaemia, diabetes, duration of diabetes and cardiovascular disease, ACE inhibitors (OR=1.27; 95% CI 1.05 to 1.55), fibrates (OR=1.57; 95% CI 1.05 to 2.35), alpha-glucosidase inhibitors (AGIs) (OR=1.85; 95% CI 1.13 to 3.02) and insulin (OR=1.80; 95% CI 1.11 to 2.93) were significantly associated with the presence of cortical cataract. Further adjusting for concurrent medication use did not alter these associations. Consistently, the four medications were also associated with a greater severity level of cortical cataract. CONCLUSION: ACE inhibitors, fibrates and AGIs were associated with increased prevalence of cortical cataract in this Asian population, independent of the presence of hypertension, hyperlipidaemia and diabetes, respectively. Whether they contribute to the risk of cortical cataract needs confirmation in longitudinal studies.

13.
Am J Ophthalmol ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31103525

RESUMO

PURPOSE: To determine the association of refractive error (RE) and its associated determinants (axial length [AL], anterior chamber depth (ACD) and corneal curvature [CC]) with the incidence and progression of diabetic retinopathy (DR). DESIGN: Population-based cohort study METHODS: A total of 1562 eyes of 840 individuals with diabetes and gradable retinal photographs (mean age [SD]: 57.0 [8.3] years, 48.2% female), from the Singapore Malay and Indian Eye Studies, at baseline (2004-2009) and follow-up (2011-2015) examinations were included in analyses. RE was calculated as sphere plus half negative cylinder, while AL, ACD and CC were assessed using optical biometry. Incident DR was defined as having no baseline DR and any DR at follow-up; incident vision-threatening DR (VTDR) as no baseline VTDR but present at follow-up; and DR progression as an increase in severity at follow-up from at least minimal baseline DR. Eye-specific data and generalized estimating equation models to account for between-eye correlation were utilized to determine the relationships between the exposures and outcomes, adjusted for traditional DR risk factors. RESULTS: At follow-up, 164 of 1273 (12.9%) had incident DR, 17 of 1542 (1.1%) eyes had incident VTDR, and 75 of 269 (27.9%) eyes with baseline DR experienced progression. A longer AL (per mm increase, risk ratio, 95% confidence interval: 0.58, 0.38, 0.88) was associated with lower risk of incident DR. No other associations were found. CONCLUSION: Our findings show that a longer AL is protective of incident DR.

14.
Sci Rep ; 9(1): 6612, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036869

RESUMO

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = -0.34 [0.05]), followed by the mild-moderate POAG group (-0.31 [0.02]) and then controls (-0.23 [0.02], PTrend = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma (PTrend = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT.

15.
Am J Ophthalmol ; 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31095951

RESUMO

PURPOSE: To describe the pattern and risk factor traits associated with visual loss (defined as either visual impairment[VI] or blindness) in a multi-ethnic Asian cohort of Malays, Indians and Chinese living in Singapore. METHODS: 10,020 participants from the Singapore Epidemiology of Eye Diseases (SEED) Study were examined between 2004-2011. All underwent standardized examinations. VI [VA<20/40 to ≥20/200] and blindness [VA<20/200]), were defined based on the U.S definition, better-seeing eye. Singapore Population Census 2010 was used to calculate age-standardized prevalence. Multiple logistic regression analysis was performed to determine the independent and joint risk factors associated with visual loss. RESULTS: Malays had higher age-standardised prevalence of best-corrected and presenting VI (5.4%; 19.9%,respectively) than Indians (3.6%; 18.0%) and Chinese (3.3%; 17.2%). Cataract was the main cause for presenting and best-corrected blindness; cataract and diabetic retinopathy were the top causes for best-corrected VI, consistently observed across the three ethnic groups. Older age, female gender, lower socioeconomic status, diabetes, systemic comorbidities and cognitive impairment were independently associated with increased risk of best-corrected visual loss (all P≤0.027). Individuals aged≥60 years with diabetes were 12.7 times (95% CI, 8.39-19.23) likely to have best-corrected visual loss, compared to younger, non-diabetic individuals. Lower income and education explained 58.1% and 23.2% of best-corrected visual loss in this population, respectively. CONCLUSION: In this urban multi-ethnic Asian population, we identified common traits associated with visual loss across Malays, Indians and Chinese. These results will be useful for the planning and designing of eye health services and strategies for Asia's rapidly developing populations living in urban communities.

16.
Br J Ophthalmol ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118184

RESUMO

BACKGROUND/AIMS: To compensate the retinal nerve fibre layer (RNFL) thickness assessed by spectral-domain optical coherence tomography (SD-OCT) for anatomical confounders. METHODS: The Singapore Epidemiology of Eye Diseases is a population-based study, where 2698 eyes (1076 Chinese, 704 Malays and 918 Indians) with high-quality SD-OCT images from individuals without eye diseases were identified. Optic disc and macular cube scans were registered to determine the distance between fovea and optic disc centres (fovea distance) and their respective angle (fovea angle). Retinal vessels were segmented in the projection images and used to calculate the circumpapillary retinal vessel density profile. Compensated RNFL thickness was generated based on optic disc (ratio, orientation and area), fovea (distance and angle), retinal vessel density, refractive error and age. Linear regression models were used to investigate the effects of clinical factors on RNFL thickness. RESULTS: Retinal vessel density reduced significantly with increasing age (1487±214 µm in 40-49, 1458±208 µm in 50-59, 1429±223 µm in 60-69 and 1415±233 µm in ≥70). Compensation reduced the variability of RNFL thickness, where the effect was greatest for Chinese (10.9%; p<0.001), followed by Malays (6.6%; p=0.075) and then Indians (4.3%; p=0.192). Compensation reduced the age-related RNFL decline by 55% in all participants (ß=-3.32 µm vs ß=-1.50 µm/10 years; p<0.001). Nearly 62% of the individuals who were initially classified as having abnormally thin RNFL (outside the 99% normal limits) were later reclassified as having normal RNFL. CONCLUSIONS: RNFL thickness compensated for anatomical parameters reduced the variability of measurements and may improve glaucoma detection, which needs to be confirmed in future studies.

17.
Hum Mol Genet ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31127295

RESUMO

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

18.
Invest Ophthalmol Vis Sci ; 60(6): 1889-1897, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042796

RESUMO

Purpose: The purpose of this study was to investigate the association between sleep (duration and quality) and symptoms of dry eye in Singapore Malay and Indian adults. Methods: This was a prospective cross-sectional study. A total of 3303 subjects aged 40 years and above from two large population-based cohorts, the Singapore Malay Eye Study-2 (n = 1191, 2011-2013) and the Singapore Indian Eye Study-2 (n = 2112, 2013-2015), were included. The presence of symptoms of dry eye was defined as having at least one of six symptoms often or all the time. Sleep questionnaires included the Epworth Sleepiness Scale, Berlin Questionnaire, STOP-bang questionnaire, and Insomnia Severity Index. Poor sleep quality was defined as meeting the respective questionnaire thresholds. General health questionnaires (including sleep duration) and standardized ocular and systemic tests were also used. Results: Of 3303 participants, 6.4% had excessive sleepiness, 20.5% had high risk for sleep apnea, 2.7% had clinical insomnia, and 7.8% had <5 hours of sleep. These sleep factors were associated with symptoms of dry eye. After adjusting for relevant demographic, medical, and social factors, the following were associated with higher odds of symptoms of dry eye: excessive sleepiness (Epworth Sleepiness Scale: odds ratio [OR] = 1.77 [1.15-2.71]), high risk of sleep apnea (Berlin Questionnaire: OR = 1.55 [1.17-2.07], STOP-Bang Questionnaire: OR = 2.66 [1.53-4.61]), clinical insomnia (Insomnia Severity Index: OR = 3.68 [2.17-6.26]) and <5 hours of sleep (OR = 1.73 [1.17-2.57], reference sleep duration 5-9 hours). Sleep apnea, insomnia, and sleep duration were each shown to be independently associated with symptoms of dry eye. Conclusion: Short sleep duration and poor quality are both significantly and independently associated with symptoms of dry eye.


Assuntos
Síndromes do Olho Seco/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Sono/fisiologia , Lágrimas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Síndromes do Olho Seco/etnologia , Síndromes do Olho Seco/etiologia , Feminino , Seguimentos , Humanos , Incidência , Índia/etnologia , Malásia/etnologia , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Singapura/epidemiologia , Apneia Obstrutiva do Sono/etnologia , Apneia Obstrutiva do Sono/fisiopatologia , Fatores de Tempo
19.
JAMA Netw Open ; 2(3): e191540, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924904

RESUMO

Importance: The association of diabetic microvascular complications such as diabetic retinopathy (DR) and diabetic kidney disease (DKD) with mortality in populations is not clear. Objective: To examine the association of DR and DKD separately and jointly with all-cause and cardiovascular disease (CVD) mortality in a multiethnic Asian population. Design, Setting, and Participants: A population-based cohort study was conducted including 2964 adults between the ages of 40 and 80 years with diabetes who participated in the Singapore Epidemiology of Eye Diseases study (baseline, 2004-2011). Data analysis was performed from January to May 2018. Exposures: Diabetic retinopathy ascertained from retinal photographs and DKD from estimated glomerular filtration rate. Main Outcomes and Measures: All-cause and CVD mortality obtained by linkage with the National Registry of Births and Deaths until May 2017. Results: Of the 2964 adults (mean [SD] age, 61.8 [10.0] years; 1464 [49.4%] female; 592 Chinese, 1052 Malay, and 1320 Indian), 29.9% of the participants had DR, while 20.7% had DKD. Over a median (interquartile range) follow-up of 8.8 (7.2-11.0) years, 610 deaths occurred (20.6%), of which 267 (9.0%) were due to CVD. In separate models, the multivariable hazard ratios for all-cause and CVD mortality were 1.54 (95% CI, 1.24-1.91) and 1.74 (95% CI, 1.27-2.40), respectively, for DR and 2.04 (95% CI, 1.64-2.56) and 2.29 (95% CI, 1.64-3.19), respectively, for DKD. In models including both DR and DKD, the subgroup with DKD alone (27.1% and 12.6%) followed by DR alone (6.5% and 5.2%) contributed substantially to the excess risk of all-cause and CVD mortality. Compared with those with no DR and DKD, the hazard ratios of all-cause and CVD mortality were 1.89 (95% CI, 1.40-2.57) and 2.26 (95% CI, 1.42-3.61), respectively, for DKD alone and 1.38 (95% CI, 1.03-1.86) and 1.64 (95% CI, 1.06-2.56), respectively, for DR alone. Hazard ratios for all-cause and CVD mortality were 2.76 (95% CI, 2.05-3.72) and 3.41 (95% CI, 2.19-5.32), respectively, for those with both DKD and DR. The relative excess risk associated with the interaction was 0.49 (95% CI, -0.29 to 1.27; P = .20) for all-cause mortality and 0.51 (95% CI, -0.83 to 1.85; P = .50) for CVD mortality. Conclusions and Relevance: These results suggest that risks of all-cause and CVD mortality were significantly higher in those with DKD and DR, but DKD was more strongly associated with excess risk. The findings underscore the importance of early identification and close monitoring and management of patients with DR and DKD to reduce the risk of death.

20.
Nutrients ; 11(3)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893833

RESUMO

The role of leptin (a hormone related to fat mass) in cognition remains equivocal. Our objective was to investigate the relationship between circulating leptin concentration and cognition in older adults, accounting for potential confounders. We categorized 1061 community-dwelling older participants ≥60 years (mean ± SD, 70.6 ± 6.4 years; 41.6% female) from the Singapore Kidney Eye Study according to quintiles of leptin concentration (≤2.64; 2.64⁻5.1; 5.2⁻8.6; 8.7⁻17.96; ≥18 ng/mL). Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Age, gender, body mass index, mean arterial pressure, smoking, alcohol, education, memory complaint, anxiodepressive disorders, circulating concentrations of 25-hydroxyvitamin D, glycosylated hemoglobin, low-density lipoprotein cholesterol, and estimated glomerular filtration rate were used as potential confounders. Participants within the lowest (Q1) and highest (Q5) leptin quintiles exhibited lower (i.e., worse) mean total AMT scores compared to those within the intermediate quintiles (Q2, Q3, and Q4). Compared to Q3 as the reference, Q1 and Q5 were associated with decreased total AMT score (respectively, ß = -0.53 p = 0.018; ß = -0.60 p = 0.036). Compared to Q3, Q5 was also associated with decreased subscores on anterograde (ß = -0.19 p = 0.020) and retrograde episodic memories (ß = -0.18 p = 0.039). We found a non-linear U-shaped relationship between circulating leptin and cognition, with both lower and higher concentrations of leptin being associated with more severe cognitive impairment in community-dwelling older Asians.


Assuntos
Disfunção Cognitiva/sangue , Leptina/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Singapura
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