Functional Annotations of Single-Nucleotide Polymorphism (SNP)-Based and Gene-Based Genome-Wide Association Studies Show Genes Affecting Keratitis Susceptibility

Yang, Xiaolin; Yang, Xiaolong; Ren, Ya-Ru; Zhuang, Xinyu; Zhang, Lei; Zhang, Xiaofeng

doi:10.12659/msm.922710

Cited by 3 publications

(1 citation statement)

References 45 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regrettably, it seems to have become standard practice to simply ignore the non-white subjects. To give 2 recent examples, a genome-wide meta-analysis of problematic alcohol use only considered 435,563 European-ancestry individuals and a genome-wide association study (GWAS) of susceptibility to keratitis only considered 337,199 subjects of European ancestry [11, 12]. Likewise, a recent analysis of the 49,960 exome-sequenced UK Biobank subjects only used information from 45,596 European subjects [3].…”

Section: Introductionmentioning

confidence: 99%

Multiple Linear Regression Allows Weighted Burden Analysis of Rare Coding Variants in an Ethnically Heterogeneous Population

Curtis

2020

Hum Hered

View full text Add to dashboard Cite

Weighted burden analysis has been used in exome-sequenced case-control studies to identify genes in which there is an excess of rare and/or functional variants associated with phenotype. Implementation in a ridge regression framework allows simultaneous analysis of all variants along with relevant covariates, such as population principal components. In order to apply the approach to a quantitative phenotype, a weighted burden score is derived for each subject and included in a linear regression analysis. The weighting scheme is adjusted in order to apply differential weights to rare and very rare variants and a score is derived based on both the frequency and predicted effect of each variant. When applied to an ethnically heterogeneous dataset consisting of 49,790 exome-sequenced UK Biobank subjects and using body mass index as the phenotype, the method produces a very inflated test statistic. However, this is almost completely corrected by including 20 population principal components as covariates. When this is done, the top 30 genes include a few which are quite plausibly associated with the phenotype, including <i>LYPLAL1</i> and <i>NSDHL</i>. This approach offers a way to carry out gene-based analyses of rare variants identified by exome sequencing in heterogeneous datasets without requiring that data from ethnic minority subjects be discarded. This research has been conducted using the UK Biobank Resource.

show abstract

Section: Introductionmentioning

confidence: 99%

Multiple Linear Regression Allows Weighted Burden Analysis of Rare Coding Variants in an Ethnically Heterogeneous Population

Curtis

2020

Hum Hered

View full text Add to dashboard Cite

show abstract

Multiple linear regression allows weighted burden analysis of rare coding variants in an ethnically heterogeneous population

Curtis

2020

Preprint

View full text Add to dashboard Cite

Weighted burden analysis has been used in exome-sequenced case-control studies to identify genes in which there is an excess of rare and/or functional variants associated with phenotype. Implementation in a ridge regression framework allows simultaneous analysis of all variants along with relevant covariates such as population principal components. In order to apply the approach to a quantitative phenotype, a weighted burden score is derived for each subject and included in a linear regression analysis. The weighting scheme is adjusted in order to apply differential weights to rare and very rare variants and a score is derived based on both the frequency and predicted effect of each variant. When applied to an ethnically heterogeneous dataset consisting of 49,790 exome-sequenced UK Biobank subjects and using BMI as the phenotype the method produces a very inflated test statistic. However this is almost completely corrected by including 20 population principal components as covariates. When this is done the top 30 genes include a few which are quite plausibly associated with the phenotype, including LYPLAL1 and NSDHL. This approach offers a way to carry out gene-based analyses of rare variants identified by exome sequencing in heterogeneous datasets without requiring that data from ethnic minority subjects be discarded. This research has been conducted using the UK Biobank Resource.

show abstract

Association of Single-Nucleotide Polymorphisms in Interleukin Genes with Microbial Keratitis in a South Indian Population

et al. 2022

View full text Add to dashboard Cite

Background: To examine the relationship between single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes and keratitis and its clinical manifestations. Methods: SNPs in IL1B, IL6, CXCL8, IL10, and IL12B were analysed. Differences in frequencies of alleles, genotypes and haplotypes between cases and controls as well as associations between SNPs and clinical variables were calculated by χ2 tests with odds ratios. Results: The minor homologous genotype in IL1B rs16944 (p = 0.036; odds ratio (OR) = 2.063, 95% confidence interval (CI): 1.048–4.061) and CXCL8 rs4073 (p = 0.041; OR = 0. 463, 95% CI: 0.224–0.956) and the heterologous genotypes in IL6 rs1800795 (p = 0.046; OR = 0.563, 95% CI: 0.326–0.972) and IL12B rs2569254 (p = 0.0446; OR = 0.557, 95% CI: 0.314–0.989) or rs730691 (p = 0.0051; OR = 0.451, 95% CI: 0.260–0.784) were associated with keratitis. The minor genotype of rs16944 was associated with severe infection (p = 0.046). The heterologous genotype in rs2569254 was associated with hospital admission, photophobia, and mode of contact lens wear (p ≤ 0.041). The heterologous genotype in rs730691 was associated with blurred vision, discharge, anterior chamber reaction, and mode of wear (p ≤ 0.047). Conclusions: This study demonstrates that SNPs in IL1B and CXCL8 are associated with risk of developing keratitis. The study also found relationships between SNPs and clinical measures of keratitis. The potential for ethnic differences in frequency of SNPs and their association with keratitis should be followed up using different populations.

show abstract

Functional Annotations of Single-Nucleotide Polymorphism (SNP)-Based and Gene-Based Genome-Wide Association Studies Show Genes Affecting Keratitis Susceptibility

Cited by 3 publications

References 45 publications

Multiple Linear Regression Allows Weighted Burden Analysis of Rare Coding Variants in an Ethnically Heterogeneous Population

Multiple Linear Regression Allows Weighted Burden Analysis of Rare Coding Variants in an Ethnically Heterogeneous Population

Multiple linear regression allows weighted burden analysis of rare coding variants in an ethnically heterogeneous population

Association of Single-Nucleotide Polymorphisms in Interleukin Genes with Microbial Keratitis in a South Indian Population

Contact Info

Product

Resources

About