Computational protocol: Thyroid Stimulating Hormone Receptor (TSHR) Intron 1 Variants Are Major Risk Factors for Graves' Disease in Three European Caucasian Cohorts

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Protocol publication

[…] Prospective power calculations in both Polish and UK cohorts demonstrated we had >99% power (α = 0.05) to detect a significant difference in allele frequencies between cases and controls, assuming an OR = 1.50 as reported previously . To ensure genotyping accuracy Hardy-Weinberg equilibrium (HWE) was calculated for all cohorts, with P<0.05 considered indicative of deviation from HWE. Allele and genotype association tests assuming recessive, dominance and co-dominance were compared between GD cases and controls using the Chi-squared test of significance within the Statistica (StatSoft Inc., Tulsa, USA) statistical package. LD between the two SNPs was measured using the pairwise LD measures D' and r2 and LD blocks were subsequently defined using the Gabriel et al algorithm . Briefly, this algorithm calculates 95% confidence intervals (CI) of D' for each pair of loci and subsequently groups sets of markers into either; “strong LD” or “strong recombination” based on the 95% CI . Strong LD is defined if the upper 95% CI has a D'>0.98 and the lower D' CI is ≥0.7 . Strong recombination is defined when the D' upper 95% CI is D'<0.9. Each LD block is defined when 95% or more of the region is classified as pairwise “strong LD”. The algorithm allows for 5% of an LD block to show some evidence of recombination . Based on this LD block definition haplotype counts of GD cases and controls were constructed and analysed for association within the computer program Haploview version 4.2, which employs an expectation maximization algorithm (http://www.broad.mit.edu/mpg/haploview) . Logistic regression analysis was performed using the SPSS statistical package (SPSS, UK) within the Polish cohorts and the PLINK statistical package was used in the UK . […]

Pipeline specifications

Software tools Statistica, Haploview, PLINK
Applications Miscellaneous, GWAS
Organisms Homo sapiens
Diseases Graves Disease