The following files describe the usage, input and output of our software for case-control association testing for samples with related individuals. The main reference for this program is Thornton T., McPeek M. S. "Case-Control Association Testing with Related Individuals: A More Powerful Quasi-Likelihood Score Test" (2007) American Journal of Human Genetics, vol 81, pp. 321-337. The MQLS program can be considered a significantly enhanced version of the CC-QLS program of Bourgain C., Hoffjan S., Nicolae R., Newman D., Steiner L., Walker K., Reynolds R., Ober C., McPeek M. S. Novel Case-Control Test in a Founder Population Identifies P-selectin as an Atopy Susceptibility Locus (2003) American Journal of Human Genetics vol 73, pp. 612-626. The MQLS program computes three different test statistics for association: the MQLS test statistic of Thornton and McPeek (2007), the WQLS test statistic of Bourgain et al. (2003), and the corrected chi-squared test statistic of Bourgain et al. (2003). These three tests are suitable for case control analysis in any sample with related individuals, including complex pedigrees, provided that their relationship is known.

The reference for the robust variance estimator (implemented in Version 1.5 and later) is Thornton T., McPeek M. S. (2010) ROADTRIPS: Case-control association testing with partially or completely unknown population and pedigree structure American Journal of Human Genetics 86: 172-184, Equation (3).

Kinship coefficients (and inbreeding coefficients for inbred pedigrees) are required to run the MQLS program. Two software programs that can be used to obtain kinship and inbreeding coefficients are

(1) The KinInbcoef software of Catherine Bourgain and Qian Zhang. The output file of the KinInbcoef program has the exact format required for the MQLS software.

or

(2) The IdCoefs software of Mark Abney. The IdCoefs software computes identity coefficients for pairs of individuals. Kinship and inbreeding coefficients can then easily be computed from the identity coefficients (the output from this software).


Acknowledgments: We gratefully acknowledge Daniel E. Weeks and Mark Kvale for their contributions to the programming.