Saddlepoint approximation

When analysing binary traits, we recommend running single-SNP analysis using a saddlepoint approximation (SPA). Classical logistic regression may result in inflation of type 1 error when testing phenotypes with case:control imbalance. The SPA implemented in LDAK guards against false positives and can robustly test SNPs for association, even when testing data with highly imbalanced case:control ratio.

The SPA is included in LDAK by default when running --logistic, for example:

./ldak.out --logistic out --bfile data ----pheno phenofile --covar covfile

The SPA can be turned off by specifying --spa-test NO, in this case LDAK switches to classical logistic regression.