ATRIUM (Association Test with Related Individuals for Untyped Markers) A C++ program for case-control association testing between a binary trait and an untyped SNP, based on genotype data from multiple typed SNPs that are in linkage disequilibrium with the untyped SNP, where information on the joint distribution of typed and untyped SNPs is obtained from an external reference panel, and where the individuals in the sample can be related. Copyright(C) 2009 Zuoheng Wang and Mary Sara McPeek Homepage: http://galton.uchicago.edu/~mcpeek/software/ATRIUM Release 1.0 October 22, 2009 The ATRIUM program can be considered an extension, to testing untyped SNPs, of the IQLS program for haplotype testing. The IQLS program will be available at http://galton.uchicago.edu/~mcpeek/software/IQLS =========================================================== License This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 3 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY of FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with this program (see file gpl.txt); if not, write to the Free Software Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA. We request that use of this software be cited in publications as Wang Z. and McPeek M. S. (2009) "ATRIUM: Testing Untyped SNPs in Case-Control Association Studies with Related Individuals". American Journal of Human Genetics 85:667-678. To contact the author: Zuoheng Wang Division of Biostatistics Yale School of Public Health 60 College St, Rm 200 New Haven, CT 06510 email: zuoheng.wang@yale.edu =========================================================== Installation instructions: 1. Download the ATRIUM package. This package contains documentation, source code, example input and output files, and a precompiled executable for the Linux platform. 2. Read the files ATRIUM_Overview, ATRIUM_Input, ATRIUM_Output and ATRIUM_Tips carefully to understand the purpose of this program and how it works. 3. Edit the Makefile as necessary according to the instructions in the Makefile. You should only need to make sure that the correct compiler and compiler options for your machine are chosen. 4. Type "make". This will build an executable program called "ATRIUM". 5. To run the executable program ATRIUM: First, prepare the input files, e.g., pedigree, markid, ibdcoef, database, and parameter (see the file ATRIUM_Input for more details). Then, to run ATRIUM with the default input filenames and settings, one need only type ./ATRIUM Alternatively, to change input filenames or settings, use flags in the command line. The following flags are available: ./ATRIUM -pheno pedigree -geno markid -ibd ibdcoef -db database -r parameter -md .4 -r2 1 -pheno pedigree Allows the user to specify the name of the phenotype input file, which also includes pedigree information. The filename defaults to "pedigree" if this flag is not used. To specify a different filename, replace "pedigree" with the appropriate filename. -geno markid Allows the user to specify the name of the genotype input file. Filename defaults to "markid". -ibd ibdcoef Allows the user to specify the name of the IBD coefficient input file. Filename defaults to "ibdcoef". -db database Allows the user to specify the name of the multilocus LD database input file, which contains information on the joint distribution of untyped SNPs with their tag SNPs in the reference panel. Filename defaults to "database". -r parameter Allows the user to specify the name of the parameter input file, which contains an estimate of the population prevalence of the binary trait. Filename defaults to "parameter". -md .4 Allows the user to specify a threshold (which must be a number between 0 and 1) for the minimum allowable amount of information on an untyped SNP, based on its tag SNPs, where information is measured by M_D (Nicolae 2006). M_D quantifies how much of the information, on a given untyped SNP, is captured by its tag SNPs (where 0 is no information and 1 is perfect information). The default value is .4. An untyped SNP is considered for testing only if its M_D value, based on its tag SNPs, is strictly greater than this threshold. -r2 1 Allows the user to specify a threshold (which must be a number between 0 and 1) for the maximum allowable r^2 between an untyped SNP and any of its tag SNPs, where r^2 is the square of the correlation coefficient. The default value is 1. An untyped SNP is considered for testing only if its maximum r^2 with any tag SNP is strictly less than this threshold. 6. Results of all untyped SNPs tested are output to a file called "ATRIUMtest.out". The top 20 untyped SNPs, i.e. the 20 untyped SNPs with the smallest p-values for association, are output to a file called "ATRIUMtest.top". The number of SNPs output to ATRIUMtest.top can be decreased or increased by the user by changing MAXTOP (currently set to 20) in the peddata.cc source file. 7. You can test the executable program ATRIUM by running it with the sample input files: pedigree, markid, ibdcoef, database and parameter. You can then compare the resulting output, which will be printed to the files ATRIUMtest.out and ATRIUMtest.top, with the correct output provided in the sample output files ATRIUMtest.out.ex and ATRIUMtest.top.ex. 8. The program stops if any errors are detected in the format of the input files.