Computational protocol: Association Analysis of Type 2 Diabetes Loci in Type 1 Diabetes

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Protocol publication

[…] For the case-control cohort, the potential population stratification was corrected using the Eigenstrat algorithm () implemented in the Eigensoft version 2.0 software (http://genepath.med.harvard.edu/∼reich/Software.htm). By the principal components analysis of population structure (), 42 case and 130 control subjects were identified and removed as outliers. Therefore, 472 type 1 diabetic case and 1,897 control subjects were analyzed for genetic association. For the family cohort, the transmission disequilibrium test was performed using the Haploview software (www.broad.mit.edu/personal/jcbarret/haploview). For a joint analysis of the two cohorts, we combined the two z scores weighted by the sample sizes. According to the statistical power calculation for a case-control study with unequal sample sizes proposed by Fleiss et al. (), the case-control cohort of 472 type 1 diabetic case and 1,897 control subjects has the statistical power equivalent to 756 case vs. 756 control subjects. The family cohort of 483 complete type 1 diabetic trios has the statistical power equivalent to 483 case vs. 483 control subjects. The joint Z score was calculated as: where Z1 is of the case-control cohort and Z2 is of the family cohort. Each Z score is equivalent to the square root of the respective χ2 value. A protective or undertransmitted minor allele corresponds to a negative Z score, whereas a risk or overtransmitted minor allele corresponds to a positive Z score. […]

Pipeline specifications

Software tools EIGENSOFT, GenePath, Haploview
Applications Population genetic analysis, GWAS
Diseases Diabetes Mellitus