Heritability And Genome-wide Association Analysis Of Near Vision In Twins

Background: With the development of aging and population growth,near vision impairment has become a serious problem affecting the quality of life of middle-aged and elderly people.In addition to environmental factors,genetic factors are also important factors affecting near vision.Several studies have explored the heritability and related single nucleotide polymorphisms(SNPs)of refractive errors,but there are differences in eye characteristics between populations in different regions,and no study has yet been conducted on the evaluation of the heritability of near vision and genome-wide association analysis(GWAS)of near vision in the Chinese population.Therefore,the study aimed to use twin samples from Qingdao,China,to evaluate the heritability of near vision and explore the SNPs,genes,and related pathways associated with near vision through GWAS analysis.Methods: The study focused on twins registered in the Qingdao Twin Registry who met the inclusion criteria.The log MAR "E" near vision chart was used to measure the near vision of the twins,and fasting venous blood samples were collected for subsequent analysis.Zygosity was determined using gender,blood type,and microsatellite DNA genotyping techniques,followed by genotyping using the Infinium Omni2.5Exome-8v1.2Bead Chip.IMPUTE2 was used to impute SNPs based on the linkage disequilibrium,and a quality control was performed before and after imputation.After adjusting for age and sex,a structural equation model was constructed using Mx software to estimate the heritability of near vision,and the power of heritability was calculated using the "umx" package in R.SNPs-based analysis was conducted using Genome-wide efficient mixed model analysis(GEMMA),and a Locus zoom plot was drawn.Gene-based analysis,pathway enrichment analysis,and cell-specific analysis were performed using VEGAS2 software,PASCAL,and FORGE2,respectively.Results: A total of 370 pairs of twins were included based on the inclusion and exclusion criteria,with an average age of 51.67 years.The median(P25,P75)for near vision was 0.4(0.25,0.70)among participants,and the within-class correlation coefficients were 0.582 for monozygotic twins and 0.355 for dizygotic twins.The best-fitting model was the AE model(additive genetic effect(A)= 59.2%,unique environmental effect(E)=40.8%).The heritability analysis had a power of over 95%.A total of 139 pairs of dizygotic twins were included in the GWAS study:(1)In the SNPs-based analysis,7,217,494 SNPs were included after quality control.The population stratification was properly adjusted(λ=0.9892).No SNP reached the significance level,but 284 SNPs exceeded the suggested significance level,with the rs147313170 of LOC124902303 on chromosome 9 shown the smallest P value,followed by rs13439937 of LOC105376313 on chromosome 9.(2)In the gene-based analysis,no gene reached the significance level,but 1,095 genes reached the suggested significance level,with the smallest P value located on LOC101927722 on chromosome 22,followed by CIB4 on chromosome 2.(3)Among the 14,885 pathways evaluated,622 pathways were significantly associated with near vision,including the integrin cell surface interactions,the ECM receptor interaction and cell adhesion molecules CAMs pathway.(4)Analysis using FORGE2 revealed that GWAS findings for near vision were enriched for DNase I hotspots in fetal muscle tissues.In the evaluation of histone marks,the near vision GWAS results were enriched for H3K27me3,H3K9me3,H3K4me3,and H3K36me3 in embryonic stem cells;for H3K9me3,H3K4me1,and H3K36me3 in induced pluripotent stem cells;and for H3K4me1,H3K4me3,and H3K9me3 in pancreatic tissue cells.Conclusion: Near vision exhibited moderate heritability in a population of middleaged and elderly twins in Qingdao.Multiple potentially near vision-related SNPs,genes,pathways,and associated cell types were identified,which could provide genetic clues for future studies of near vision.