Dataset Information

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

ABSTRACT: Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h²?=?0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N?=?14,151 and replication N?=?5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P?=?2.8?×?10^-16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P?=?1.7?×?10^-19), TMPRSS5 (rs4936279, P?=?2.5?×?10^-10), LINC01412 (rs16823886, P?=?1.3?×?10^-9), GLTSCR1 (rs1005911, P?=?9.8?×?10^-9), and COMMD1 (rs62149908, P?=?1.2?×?10^-8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.

SUBMITTER: Yonova-Doing E

PROVIDER: S-EPMC7733496 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Yonova-Doing Ekaterina E Zhao Wanting W Igo Robert P RP Wang Chaolong C Sundaresan Periasamy P Lee Kristine E KE Jun Gyungah R GR Alves Alexessander Couto AC Chai Xiaoran X Chan Anita S Y ASY Lee Mei Chin MC Fong Allan A Tan Ava G AG Khor Chiea Chuen CC Chew Emily Y EY Hysi Pirro G PG Fan Qiao Q Chua Jacqueline J Chung Jaeyoon J Liao Jiemin J Colijn Johanna M JM Burdon Kathryn P KP Fritsche Lars G LG Swift Maria K MK Hilmy Maryam H MH Chee Miao Ling ML Tedja Milly M Bonnemaijer Pieter W M PWM Gupta Preeti P Tan Queenie S QS Li Zheng Z Vithana Eranga N EN Ravindran Ravilla D RD Chee Soon-Phaik SP Shi Yuan Y Liu Wenting W Su Xinyi X Sim Xueling X Shen Yang Y Wang Ya Xing YX Li Hengtong H Tham Yih-Chung YC Teo Yik Ying YY Aung Tin T Small Kerrin S KS Mitchell Paul P Jonas Jost B JB Wong Tien Yin TY Fletcher Astrid E AE Klaver Caroline C W CCW Klein Barbara E K BEK Wang Jie Jin JJ Iyengar Sudha K SK Hammond Christopher J CJ Cheng Ching-Yu CY

Communications biology 20201211 1

Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h<sup>2</sup> = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic ...[more]

PMID: 33311586

Similar Datasets

Project description:ObjectiveWe investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.MethodsWe carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.Results7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.ConclusionsOur results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.

Dataset Information

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Publications

Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets