# Perform association tests between phenotype risk scores and genotypes

Source:`R/genetic_association.R`

`getGeneticAssociations.Rd`

The association test for each disease-variant pair is based on a linear model, with the phenotype risk score as the dependent variable.

## Usage

```
getGeneticAssociations(
scores,
genotypes,
demos,
diseaseVariantMap,
lmFormula,
modelType = c("genotypic", "additive", "dominant", "recessive"),
level = 0.95,
dopar = FALSE
)
```

## Arguments

- scores
A data.table of phenotype risk scores. Must have columns

`person_id`

,`disease_id`

,`score`

.- genotypes
A matrix or 'BEDMatrix' object containing genetic data, with rownames corresponding to

`person_id`

s in`demos`

and`scores`

, and colnames corresponding to`variant_id`

s in`diseaseVariantMap`

.- demos
A data.table of characteristics for each person in the cohort. Must have column

`person_id`

.- diseaseVariantMap
A data.table indicating which genetic variants to test for association with phenotype risk scores for which diseases. Must have columns

`disease_id`

and`variant_id`

.- lmFormula
A formula representing the linear model (excluding the term for genotype) to use for the association tests. All terms in the formula must correspond to columns in

`demos`

.- modelType
A string indicating how to encode genotype in the model.

- level
A number indicating the level of the confidence interval. Default is 0.95.

- dopar
Logical indicating whether to run calculations in parallel if a parallel backend is already set up, e.g., using

`doParallel::registerDoParallel()`

. Recommended to minimize runtime.

## Value

A data.table of statistics for the association tests (if a model fails to converge, NAs will be reported):

`disease_id`

: Disease identifier`variant_id`

: Variant identifier`n_total`

: Number of persons with non-missing genotype data for the given variant.`n_wt`

: Number of persons homozygous for the wild-type allele.`n_het`

: Number of persons having one copy of the alternate allele.`n_hom`

: Number of persons homozygous for the alternate allele.`beta`

: Coefficient for the association of genotype with score`se`

: Standard error for`beta`

`pval`

: P-value for`beta`

being non-zero`ci_lower`

: Lower bound of the confidence interval for`beta`

`ci_upper`

: Upper bound of the confidence interval for`beta`

If `modelType`

is "genotypic", the data.table will include separate
statistics for heterozygous and homozygous genotypes.

## Examples

```
library('data.table')
library('BEDMatrix')
# map ICD codes to phecodes
phecodeOccurrences = getPhecodeOccurrences(icdSample)
# calculate weights
weights = getWeights(demoSample, phecodeOccurrences)
# OMIM disease IDs for which to calculate phenotype risk scores
diseaseId = 154700
# map diseases to phecodes
diseasePhecodeMap = mapDiseaseToPhecode()
# calculate scores
scores = getScores(weights, diseasePhecodeMap[disease_id == diseaseId])
# map diseases to genetic variants
nvar = 10
diseaseVariantMap = data.table(disease_id = diseaseId, variant_id = paste0('snp', 1:nvar))
# load sample genetic data
npop = 50
genoSample = BEDMatrix(system.file('extdata', 'geno_sample.bed', package = 'phers'))
#> Extracting number of samples and rownames from geno_sample.fam...
#> Extracting number of variants and colnames from geno_sample.bim...
colnames(genoSample) = paste0('snp', 1:nvar)
rownames(genoSample) = 1:npop
# run genetic association tests
genoStats = getGeneticAssociations(
scores, genoSample, demoSample, diseaseVariantMap, lmFormula = ~ sex,
modelType = 'additive')
```