ONETOOL has four main analysis modules: informatics and quality control (InfoQC), trait analysis, linkage analysis and association analysis.

• InfoQC analysis

• Trait analysis

• Linkage analysis

• Association analysis

InfoQC analysis module provides the options for the various information and QC procedures.

Category	Available analysis
Variant information	MAF - Minor allele frequency HWE - Hardy-Weinberg Equlibrium PCA - Principle component analysis Fstatistics - Wright's fixation index to describe population structure Ts/Tv - Ratio of transition (changes from A <-> G and C <-> T) to transversion (changes from A <-> C, A <-> T, G <-> C or G <-> T)
Sample information	Het - Heterozygote Het/Hom - Ratio of heterozygote and homozygote
Pedigree information	Descriptive and summary statistics including means, standard deviations; family, sibship and pedigree sizes; and counts of each type of relative pair (PEDINFO in S.A.G.E. package) Pedigree plot Lists of each type of relative pair (PedWiz)
Error detection	Mendelian inconsistencies of markers
Relatedness matrix	Kinship Indentity-by-state(IBS) Genetic relationship matrix(GRM)

Trait analysis module provides the first step analyses to test for the causal relationship between genetic variants and a trait of interest.

Category	Available analysis
Familial aggregation	Multivariate familial correlations with their asymptotic standard errors (FCOR in S.A.G.E. package)
Heritability	Based on kinship, IBS, GRM
Segregation analysis	Commingling analysis - Fit mixtures of two or three normal distributions Fit and test Mendelian segregation models in the presence of residual familial correlations, generate type robability files for model-based linkage analysis (SEGREG in S.A.G.E. package)

Linkage analysis module implements the analysis methods to test for co-segregation of a chromosomal region and a trait of interest.

Category	Available analysis
Model-based	Single-marker/two-point (LODLINK in S.A.G.E. package) LOD scores and recombination fractions between a marker and trait, test of linkage
Model-free	Multi-marker, modeling LD (Whittemore and Halpern NPL pairs method in MERLIN) P-value assuming normal approximation, Kong and Cox delta, LOD score and p-value

Association analysis module provides many different family-based association tests between trait(s) and both single variant and gene-based.

Category	Available analysis
Single variant	Generalized score test, regression, Fisher's exacttest Transmission diseqilibrium test - TDT/SDT Likelihood ratio test - MQLS/FLS/MFQLS Linear mixed model test - GEMMA
Gene-based	collapsing - CMC burden test - PEDCMC/wSum/aSum variable threshold method - VT/famVT kenel method - KBAC/SKAT/SKATO/FARVAT/mFARVAT/FARVATx combined - PEDGENE