Computational protocol: Investigating the relationship between UMODL1 gene polymorphisms and high myopia: a case–control study in Chinese

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Protocol publication

[…] In the initial study, 58 tag SNPs were selected from an 86-kb genomic region comprising the UMODL1 gene and its 3-kb flanking regions (both upstream and downstream) by Haploview []. The selection was based on the Han Chinese data from the International HapMap Project (release 23a, phase II; http://www.hapmap.org/) [] with the following criteria: pairwise tagging algorithm, r2 ≥ 0.8, minor allele frequency (MAF) >0.2 and forced inclusion of SNPs that had been tested in the Japanese study. A non-synonymous SNP (rs3819142) was added at a later stage and genotyped for both sample sets because it was in moderate linkage disequilibrium (LD; r2 =0.6) with rs220170, which was one of the SNPs constituting a putatively positive haplotype from the initial study. [...] Ocular data were analyzed using the SPSS package (version 11.5; SPSS Inc.). Subjects were classified as affected (cases) or unaffected (controls). High myopia was analyzed as a dichotomous trait and a quantitative trait separately. Subset analysis was also performed by defining cases with increasingly restrictive thresholds of refractive error in order to fully explore the genotype data (Sample Sets 1 and 2). Hardy-Weinberg equilibrium (HWE) was tested for controls and cases separately by Fisher’s exact test executed within Plink (version 1.07) []. SNPs that were not in HWE were excluded from subsequent association analysis. Haplotype blocks were constructed by Haploview with an algorithm known as the solid spine of linkage disequilibrium (SSLD) []. Single-marker and haplotype analyses were performed with three packages: Haploview, Plink and Beagle (ver. 3.0) [-]. Multiple testing was corrected by 10,000 permutations to generate empirical P values (Pemp). Localized haplotype clusters that were found significantly associated with high myopia by Beagle were further analyzed using the cluster2haps program to identify the haplotypes and SNPs defining the clusters [].The SPREG program [] was used to analyze secondary phenotypes because the case–control subjects were not collected from a random population. SPREG implements valid and efficient statistical methods for analyzing secondary phenotypes collected in case–control association studies. It used a modified linear regression method to analyze secondary phenotypes including axial length (AXL), anterior chamber depth (ACD), lens thickness (LT) and corneal power (CP). False discovery rate (FDR) was used to correct for multiple comparisons within a given secondary phenotype []. […]

Pipeline specifications

Software tools Haploview, PLINK, BEAGLE
Databases International HapMap Project
Application GWAS
Diseases Myopia