Computational protocol: Common Variants in CRP and LEPR Influence High Sensitivity C-Reactive Protein Levels in North Indians

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Protocol publication

[…] Linear-regression was performed assuming an additive model to determine association of variants with hsCRP levels. Samples with hsCRP level >10 µg/mL were excluded from the analysis. hsCRP concentrations were natural logarithm transformed to ensure a normal distribution. To assess independent contribution of each variant, stepwise multivariate linear regression models with age, sex, and body mass index (BMI) as covariates were constructed. Variants with a P<0.05 were retained in the forward stepwise-selection models. Analyses were first carried out in non-diabetic subjects not taking lipid-lowering drugs, adjusting for age, sex, BMI, and smoking/tobacco chewing and then in T2D patients and all subjects, additionally adjusting for diseases status and medication as appropriate.Bonferroni correction was used to account for multiple testing and a P<8.6×10−4 was considered significant after correcting for number of independent variants α = 0.05/58). Pairwise linkage disequilibrium (LD) between the SNPs for all the genes was determined using Haploview 4.0 (). Association of haplotypes with frequency >0.1 was examined through sliding window approach using PLINK by adjusting for age, sex, BMI, smoking/tobacco chewing, diseases status, and medication, as appropriate, based on 10,000 permutations. Fixed and random effect meta-analysis was performed for the two replicated variants, in non-diabetic subjects, T2D patients and all subjects.Statistical power of the study was evaluated using QUANTO version 1.2 . Our study had 78% and 92% power to detect association for a variant with MAF = 0.2 and effect size of 0.3 µg/mL for additive model for non-diabetic subjects and for all subjects analyzed together respectively. Statistical analyses were performed using SPSS version 17.0 (SPSS, Chicago, IL) and PLINK . […]

Pipeline specifications

Software tools Haploview, PLINK
Application GWAS
Organisms Homo sapiens
Diseases Diabetes Mellitus, Machado-Joseph Disease