To calculate power at given sample size assuming equal case control samples (1000 cases, 1000 controls), at an effect size of odds ratio equals 2 for rare variants, 1 for common variants, evaluated at \(\alpha=0.05\):

spower LOGIT KIT.gdat -a 2 --sample_size 2000 --alpha 0.05 -v2 -o K1AP

To calculate sample size assuming equal case control samples given 80% power and using the same setup as above:

spower LOGIT KIT.gdat -a 2 --power 0.8 --alpha 0.05 -v2 -o K1AS

To view results

spower show K1AP.csv power*
spower show K1AS.csv sample_size*

A variable effect model below will assign to rare variants odds ratio \(\in(1,3)\) depending on the MAF of rare variants:

spower LOGIT KIT.gdat -a 1 -A 3 --sample_size 2000 --alpha 0.05 -v2 -o K1AP

Adding effects for common variants, fixed to odds ratio 1.2:

spower LOGIT KIT.gdat -a 1 -A 3 -c 1.2 --sample_size 2000 --alpha 0.05 -v2 -o K1AP
spower LOGIT KIT.gdat -a 1 -A 3 -c 1.2 --power 0.8 --alpha 0.05 -v2 -o K1AS

Now based on the basic example, we change definition for rare variants to MAF > 5%:

spower LOGIT KIT.gdat -a 2 --def_rare 0.05 --sample_size 2000 --alpha 0.05 -v2 -o K1AP

Power of the test boosts significantly, although it is not a reasonable setup to apply aggregated rare variant analysis to high frequency variants like in this example. There is usually adequate power to detect common variants association when analyzed individually.

It is often the case that not all functional rare variants are directly causal to the phenotype. To add such non-causal “noise” to data and evaluate the impact on power / sample size, we can set a random set of 50% variants to be non-causal (-P option) and be included in analysis. Since the assignment of non-causal variant is random, the final estimate should be based on the average of multiple replicates, for example 100 replicates:

spower LOGIT KIT.gdat -a 2 --def_valid_locus 3 1000 --sample_size 2000 --alpha 0.05 -P 0.5 -r 100 -v2 -o K1APP
spower LOGIT KIT.gdat -a 2 --def_valid_locus 3 1000 --power 0.8 --alpha 0.05 -P 0.5 -r 100 -v2 -o K1APS
spower show K1APP.csv power power_std

Note that standard deviation for the 100 replicates is also calculated and can be displayed.

To calculate power at given sample size assuming equal case control samples (1000 cases, 1000 controls), at an effect size of PAR equals 5% for rare variants, 1% for common variants, evaluated at \(\alpha=0.05\):

spower PAR KIT.gdat -a 0.05 -c 0.01 --sample_size 2000 --alpha 0.05 -v2 -o K1AP

To calculate sample size assuming equal case control samples given 80% power and using the same setup as above:

spower PAR KIT.gdat -a 0.05 -c 0.01 --power 0.8 --alpha 0.05 -v2 -o K1AS

To view results

spower show K1AP.csv power*
spower show K1AS.csv sample_size*

A variable effect model below will assign site specific PAR to deleterious rare variants depending on the MAF of rare variants:

spower PAR KIT.gdat -a 0.05 --PAR_variable --sample_size 2000 --alpha 0.05 -v2 -o K1AP
spower PAR KIT.gdat -a 0.05 --PAR_variable --power 0.8 --alpha 0.05 -v2 -o K1AS

The use of -P and -r options to model the effect of non-causal variants was previously introduced in logit model. The same idea applies to PAR model. See section above for details.

To calculate power at given sample size for randomly ascertained QT samples of 2000 unrelated individuals, at an effect size of \(0.25\sigma\), evaluated at \(\alpha=0.05\):

spower LNR KIT.gdat -a 0.25 --sample_size 2000 --alpha 0.05 -v2 -o K1AP # power 0.22

To calculate sample size assuming equal case control samples given 80% power and using the same setup as above:

spower LNR KIT.gdat -a 0.25 --power 0.8 --alpha 0.05 -v2 -o K1AS # sample size 10806

A variable effect model below will assign to rare variants mean shift \(\in(0.1, 0.5)\) depending on the MAF of rare variants:

spower LNR KIT.gdat -a 0.1 -A 0.5 --sample_size 2000 --alpha 0.05 -v2 -o K1AP # 0.289

Adding effects for common variants, fixed mean shift to 0.15:

spower LNR KIT.gdat -a 0.1 -A 0.5 -c 0.15 --sample_size 2000 --alpha 0.05 -v2 -o K1AP # 0.86
spower LNR KIT.gdat -a 0.1 -A 0.5 -c 0.15 --power 0.8 --alpha 0.05 -v2 -o K1AS # 1966

Now based on the basic example, we change definition for rare variants to MAF > 5%:

spower LNR KIT.gdat -a 0.25 --def_rare 0.05 --sample_size 2000 --alpha 0.05 -v2 -o K1AP # 0.946

Power of the test boosts significantly, although it is not a reasonable setup to apply aggregated rare variant analysis to high frequency variants like in this example. There is usually adequate power to detect common variants association when analyzed individually.

For example we set a random set of 50% variants that would not contribute to the quantitative phenotype, but will be included in analysis as noise and as a result larger sample size is required to achieve the same power. Since each time a random proportion of variants are considered non-causal, the final estimate should be based on average of multiple replicates, for example 100 replicates:

spower LNR KIT.gdat -a 0.5 --def_valid_locus 3 1000 --sample_size 20000 --alpha 0.05 -P 0.5 -r 100 -v2 -o K1APP --jobs 8 # power 0.8632
spower LNR KIT.gdat -a 0.5 --def_valid_locus 3 1000 --power 0.8 --alpha 0.05 -P 0.5 -r 100 -v2 -o K1APS --jobs 8 # sample size 17420.4501268
spower show K1APP.csv power*
spower show K1APS.csv *size*

Note that standard deviation for the 100 replicates is also calculated and can be displayed with wildcard symbol “*” in spower show command.