The superior of SNPTEST to SNPTEST-BG demonstrates that incorporating the uncertainty of imputation can improve association power.
Guan & Stephens [24] studied the effect of imputation accuracy on association power, however their study was performed solely on the software BIMBAM.
Our results show that in regions with medium or high LD level, the imputation-based test can improve the association power even under moderate imputation AR (69.2% under medium LD level).
Additional file 1: Association power curves.
These imputed variants enhanced genomic coverage, resulting in increased association power [ 15], enabling us to perform in silico fine mapping in imputation-based association studies.
This is, however, not unexpected, given SNP chip content and association power limitations brought about by the sample sizes employed (Table 1).
Genotype uncertainty metrics for imputed genetic variants or for sequencing-derived variants could be incorporated as weights in different statistical tests, instead of filtering out variants with low imputation or quality scores, to increase association power as shown by (52).
More importantly, larger reference panels increase the computational burden of imputation, which may compel some investigators to use smaller panels at the cost of imputation accuracy and association power.
A recent simulation study found that association power and mean imputation R have a roughly linear relationship with a slope near 1.0 (Zheng et al. 2011), which suggests that using the HM3 panel in place of the GMB panel would cause only a small loss of power in an imputation-based association scan.
These data require confirmation in a second, larger sized cohort to be certain of an association (power calculations based on this pilot study indicate a PTLD and non-PTLD transplant group size of 105 subjects would provide 80% power, 95% CI, OR=2.5) and further analysis of soluble TNF levels may offer some information on the functional activity of these polymorphic alleles.
