# NCBI dbGaP analysis accession: pha002854 # Name: Genome Wide Association Study of Multiple Sclerosis # Description: Quality Control Sample and SNP filtering was done by investigators.TDT association analysis was replicated in pre-compute at NCBI. Quality control A total of 1,003 parent-affected child trios were initially identified for genotyping. After tests for DNA quality and quantity and Mendelian errors (using the Sequenom fingerprint SNP results), a total of 960 trios were genotyped using both Affymetrix chips. Results due to systematic errors and families with false paternity were removed. Preliminary analysis uncovered a relationship between the BRLMM-generated quality score (this score is the output for each SNP genotype call by the BRLMM program), and genotypes with Mendelian errors ( 0.3 as defined in http://www.broad.mit.edu/gen_analysis/genotyping/brlmm_affy_ncrr.html, but they contributed over 20% of the genotypes with Mendelian errors). Therefore, any genotype with a BRLMM quality score > 0.3 was removed. The results then underwent quality control procedures implemented by a software package (WASP; Whole-genome Association Study Pipeline) that included the examination of SNP and sample genotyping efficiency, allele frequencies, checks of Mendelian errors, and sex-assignment discrepancies (based on available chromosome X genotypes), and tests of Hardy-Weinberg Equilibrium. We used the Graphical Representation of Relationships (GRR) program7 to test for relationships between samples and to detect sample switches, duplications, or contamination. Potential population stratification was examined as follows. From the 334,923 SNPs, we chose 1000 (with > 1Mb physical spacing) that had maximal chi-square differences in allele frequency between HapMap populations (500 for the CEU/YRI comparison, and 500 for the CEU/CHB+JPT comparison). The analysis International Multiple Sclerosis Genetic Consortium, N Engl J Med 2007;3576 (using the STRUCTURE program8) was seeded with data from unrelated individuals (60 CEU, 60 YRI, 45 CHB, 45 JPT). No significant stratification was observed. Further, we used the results of these analyses to determine if any individual appeared to be of non-European descent. We removed any individual who had a probability of SNP exclusion criteria To advance to the whole-genome association study, SNPs had to pass the following quality control criteria: not mapping to multiple locations in the genome (3,605 SNPs excluded); a > 95% genotype call rate in the total 2,880 (960 trio) samples (58,435 SNPs excluded); allele frequency (MAF) > 0.005 in the parents (59,887 SNPs excluded); Hardy Weinberg equilibrium with P > 1 x 10-4 in parents (16,881 SNPs excluded); > 99% genotype call rate if the SNP had a MAF # Method: For each marker, counts of transmitted (T) and non-transmitted (NT) alleles were calculated for heterozygous parents in all complete trios (that is, trios for which genotype data was available for the mother, father and child). A Chi-squared statistic with 1-df was defined as (T-NT)^2 / (T+NT) and its significance was evaluated with reference to a standard Chi-squared distribution. # Human genome build: 37 # dbSNP build: 132 # SNP ID: Marker accession # P-value: testing p-value # Chr ID: chromosome # Chr Position: chromosome position # ss2rs: ss to rs orientation. +: same; -: opposite strand. # rs2genome: Orientation of rs flanking sequence to reference genome. +: same orientation, -: opposite. # Allele1: genomic allele 1 # Allele2: genomic allele 2 # pHWE: p-value from HWE testing # Transmit allele1: number of transmitted allele 1 # Transmit allele2: number of transmitted allele 2 # No. Informative Chrs: number of informative chromosomes