Yaxing Wang

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR) = 1.22; P = 5.33 × 10−12), rs3753841 in COL11A1 (per-allele OR = 1.20; P = 9.22 × 10−10) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR = 1.50; P = 3.29 × 10−9). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Retinal vessel diameter in normal and glaucomatous eyes: the Beijing eye study.

Purpose:u2002 To assess retinal vessel diameter in adult Chinese with and without glaucoma.

Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations

Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent. We have followed up on all suggestive signals of association with CCT (P < 10(-4)) from the previously reported meta-analysis comprising Indians and Malays in a sample of Chinese individuals (n= 2681). In the combined sample (n= 7711), strong evidence of association was observed at four novel loci: IBTK on chromosome 6q14.1; CHSY1 on chromosome 15q26.3; and intergenic regions on chromosomes 7q11.2 and 9p23 (8.01 × 10(-11) < λ(GC) corrected P(meta) < 8.72 × 10(-8)). These four new loci explain an additional 4.3% of the total CCT variance across the sample cohorts over and above that of previously identified loci. We also extend on a previous finding at a fifth locus (AKAP13) where a new single-nucleotide polymorphism (rs1821481, P(meta) = 9.99 × 10(-9)) was found to be significantly more informative compared with the previously reported rs6496932 (P(meta) = 3.64 × 10(-5)). Performing association analysis in Asians may lead to the discovery of ethnic-specific genes that control CCT, offering further mechanistic insights into the regulation of CCT. In addition, it may also provide several candidate genes for interrogation for POAG, keratoconus and possible racial/ethnic variations.

Retinal nerve fibre layer thickness measured by Spectralis spectral‐domain optical coherence tomography: The Beijing Eye Study

The aim of this study was to measure retinal nerve fibre layer thickness (RNFLT) and its associated factors in a population‐based setting.

ABCC5, a Gene That Influences the Anterior Chamber Depth, Is Associated with Primary Angle Closure Glaucoma

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect sizeu200a=u200a−0.045 mm, Pu200a=u200a8.17×10−9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele ORu200a=u200a1.13 [95% CI: 1.06–1.22], Pu200a=u200a0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele ORu200a=u200a1.30, Pu200a=u200a7.45×10−9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Size of the neuroretinal rim and optic cup and their correlations with ocular and general parameters in adult Chinese: the Beijing eye study

Aim: To measure the size of the neuroretinal rim, the major variable in the quantitative analysis of the optic nerve head, and its correlations in adult Chinese in a population based setting. Methods: The Beijing eye study—a population based, cross sectional cohort study—included 4439 subjects from among 5324 of age of 40+ years invited to participate (response rate 83.4%). This study included a random sample of 781 subjects with normal intraocular pressure (IOP), normal visual fields, and a normal optic nerve head; and a random sample of 84 subjects with an IOP >21 mm Hg. Colour optic disc photographs (30°) were examined morphometrically. Results: In the normal group, the mean (SD) neuroretinal rim area was 1.70 (0.30) mm2. It was significantly correlated with optic disc area (rim areau200a=u200a0.43*disc area+0.67; p<0.001). It was not significantly associated with age, sex, or a known diagnoses of diabetes mellitus, arterial hypertension or hypotension, hyperlipidaemia, coronary heart disease, or cerebral haemorrhage. Conclusions: In adult Chinese, the neuroretinal rim area measures 1.70 (0.30) mm2 on optic disc photographs. It is statistically independent of age. Compared with data from studies in Western countries, the neuroretinal rim is larger in adult Chinese than in adult white populations, corresponding to a larger optic disc size in the Chinese.

Lack of Association Between Primary Angle-Closure Glaucoma Susceptibility Loci and the Ocular Biometric Parameters Anterior Chamber Depth and Axial Length

PURPOSEnThree susceptibility loci for primary angle-closure glaucoma (PACG) were recently identified: PLEKHA7 rs11024102, COL11A1 rs3753841, and rs1015213 located in the intergenic region between PCMTD1 and ST18. The purpose of this study was to investigate the associations of these loci with the ocular biometric parameters anterior chamber depth (ACD) and axial length (AL).nnnMETHODSnGenotype and ocular biometric data were available for four population-based studies, including three from Singapore (Singapore Chinese Eye Study, Singapore Malay Eye Study, and Singapore Indian Eye Study) and one from China (Beijing Eye Study), exceeding 7000 participants. ACD and AL were measured using the IOLMaster for the Singapore cohorts and optical low-coherence reflectometry (Lenstar 900 Optical Biometer) for the Beijing cohort. Five readings were obtained for each participant and the average was computed. Analysis excluded any eye that was pseudophakic or aphakic.nnnRESULTSnACD measurements and genotype data of the three loci were available for 7245, 7243, and 7239 subjects, respectively. We noted nominal evidence of association between single nucleotide polymorphism (SNP) rs1015213 (PCMTD1-ST18) and a shallower ACD when all data were meta-analyzed (β = -0.033, P = 0.021). When multiple testing was considered, the observation was nonsignificant. There was no association between ACD and rs11024102 (PLEKHA7) or rs3753841 (COL11A1). We did not observe significant associations between AL and any of the three SNPs.nnnCONCLUSIONSnThe lack of association between the PACG susceptibility loci with ACD or AL suggests that predilection to PACG may be mediated by factors other than shallow anterior chamber or short eyeball length.

Frequency of retinal macroaneurysms in adult Chinese: the Beijing Eye Study.

A retinal arterial macroaneurysm is an acquired retinal vascular abnormality, typically a solitary, round or fusiform aneurysm arising in one of the four major branch retinal arteries in the paramacular area. According to hospital-based investigations, most patients in whom this pathological condition develops are in their sixth or seventh decade of life and have a history of systemic hypertension, ophthalmoscopic evidence of retinal arteriolar sclerosis or both. Visual loss is caused by exudation or bleeding from the aneurysm. Massive retinal bleeding from a ruptured aneurysm can be confined to the …

Frequency of non-arteritic anterior ischaemic optic neuropathy in adult Chinese: the Beijing Eye Study.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is an acute optic neuropathy occurring predominantly in small optic nerve heads in elderly patients.1–3 It has been debated which factors, other than old age and a small optic disc size, predispose to the disease. Data on the prevalence of NAION in the general population has so far been scarce.4,5 They have been completely missing for the Chinese. Therefore, the aim of this study was to evaluate the prevalence of optic nerve damage with the features of a preceding NAION in the Beijing Eye Study.nnThe Beijing Eye Study is a population-based cohort study in Northern China.6 The Medical Ethics Committee of the Beijing Tongren Hospital approved the study protocol and all participants gave their informed consent, according to the …

MACULAR BRUCH MEMBRANE DEFECTS IN HIGHLY MYOPIC EYES: The Beijing Eye Study.

Purpose: To examine prevalence and associations of macular Bruch membrane defects (MBMDs) in a population-based setting. Design: Population-based cross-sectional study. Methods: The Beijing Eye Study 2011 included 3,468 subjects who underwent a detailed ophthalmic examination including spectral domain optical coherence tomography with enhanced depth imaging of the macula. Macular Bruch membrane defects were defined as an interruption of Bruch membrane on the optical coherence tomography images in the macular region. Results: Macular Bruch membrane defects could be detected only in highly myopic eyes (defined as refractive error of ⩽−6 diopters or axial length of ≥26.5 mm) with a prevalence of 17/164 (10.4%, 95% confidence interval [CI], 5.7%–18.1%). Best-corrected visual acuity <0.05 was found in 5 (29%) of 17 eyes with MBMDs, and in 7 (41%) eyes, visual acuity was <0.3 and ≥0.05. In the MBMD region, retinal pigment epithelium and choriocapillaris were completely lost, and the deep and middle layers of the retina and the choroid were almost completely absent. In the MBMD region, mean retinal thickness was 153 ± 57 &mgr;m (mean ± SD) and choroidal thickness was 12.7 ± 28.1 &mgr;m. On the fundus photographs, MBMDs appeared as whitish areas with round borders. In multivariate regression analysis, presence of MBMD was significantly associated only with longer axial length (Odds ratio: 3.87; 95% CI, 1.64–9.14). Conclusion: Macular Bruch membrane defects with a prevalence of approximately 10% in highly myopic eyes are associated with a complete loss of retinal pigment epithelium and choriocapillaris, an almost complete loss of photoreceptors and choroid, and marked reduction in visual acuity. Macular Bruch membrane defects may be added to the panoply of features of myopic maculopathy.