The National Center for Biotechnology Information (NCBI) has been managing and distributing the large database of Genotypes and Phenotypes (dbGaP) for scientific investigation of various human diseases [32]. In order to demonstrate the application of the proposed method, we conducted statistical analysis on the Study of Addiction: Genetics and Environment (SAGE) data [33], http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1. The institutional review board of the University of Michigan has approved this secondary data analysis project (HUM00084927). The SAGE is a case-control study that aggregated together the data from three large scale studies in the substance abuse field: the Collaborative Study on the Genetics of Alcoholism (COGA), the Family Study of Cocaine Dependence (FSCD), and the Collaborative Genetic Study of Nicotine Dependence (COGEND). The total number of individuals with individual level data available is 4121. Each individual was genotyped using the Illumina Human 1M-Duo beadchip which contains over 1 million SNP markers.
