library(gait)
library(plyr)

1 About

These pages show particular examples to illustrate the ‘solarius’ package’s behaviour with large datasets. In particular, these examples were generated with the GAIT (Genetic Analysis of Idiopathic Thrombophilia) dataset. The GAIT Project included 397 individuals from 21 extended Spanish families (mean pedigree size = 19) (J. C. Souto et al. (2000)). A genome-wide set of 307,984 SNPs was typed in all of the participants using the Infinium 317 k Beadchip on the Illumina platform (San Diego, CA, USA).

We selected 3 specific examples where we could compare the results obtained with the ‘solarius’ package with those previously obtained and published in Sabater2012 and Souto2014. The 3 selected phenotypes were the FXI levels in blood, the BMI and the Thrombosis affection.

2 Load packages

library(solarius)
library(gait)

3 Load GAIT1 data

We first load our data and properly transform the phenotypes under study.

pdat  <- gait1.phen()
pdat <- mutate(pdat, 
  tr_FXI = FXI_T * 5.1,
  ln_bmi = log(bmi),  
  tr_bmi = 6.1 * ln_bmi)

gait1.snpfiles <- gait1.snpfiles()

mibddir <- gait1.mibddir()
cores <- 64

4 FXI

We first applied the main models of association and linkage of the package to the FXI levels in blood. The FXI phenotype has already been studied in the same dataset as described in Sabater-Lleal et al. (2012). This example aims to illustrate the proper behaviour of the solarius package by replicating these former results.

The polygenic model that estimates the heritability of the FXI levels in blood is described by M.F11.

# trait previously transformed, only significant covariates
M.F11 <- solarPolygenic(tr_FXI ~ AGE, pdat, covtest=T)
M.F11
## 
## Call: solarPolygenic(formula = tr_FXI ~ AGE, data = pdat, covtest = T)
## 
## File polygenic.out:
##  Pedigree:    dat.ped 
##  Phenotypes:  dat.phe 
##  Trait:       tr_FXI                Individuals:  343 
##  
##           H2r is 0.3661086  p = 0.0000264  (Significant) 
##         H2r Std. Error:  0.1041961 
##  
##            C2 is 0.1708059  p = 0.0119484  (Significant) 
##          C2 Std. Error:  0.0816026  
##  
##                                       AGE  p = 2.2310194e-08  (Significant) 
##  
##  76 pedigrees merged into 68 pedigree-household groups 
##  
##  Proportion of Variance Due to All Final Covariates Is 
##                0.0694126 
##  
##  Loglikelihoods and chi's are in tr_FXI/polygenic.logs.out 
##  Best model is named housepoly and null0 
##  Final models are named housepoly, house, poly, spor, nocovar 
##  Initial sporadic and polygenic models are s0 and p0 
##  Initial household and household polygenic models are h0 and hp0 
##  Constrained covariate models are named no<covariate name> 
##  
##  Residual Kurtosis is 0.1813, within normal range

The model of association is described by A.F11

A.F11 <- solarAssoc(tr_FXI ~ AGE, pdat, 
  genocov.files = gait1.snpfiles$genocov.files, 
  snplists.files = gait1.snpfiles$snplists.files, 
  snpmap.files = gait1.snpfiles$snpmap.files, 
  cores = cores)
summary(A.F11)
## 
## Call: solarAssoc(formula = newTrait ~ AGE, data = pdat, genocov.files = gait1.snpfiles$genocov.files, 
##     snplists.files = gait1.snpfiles$snplists.files, snpmap.files = gait1.snpfiles$snpmap.files, 
##     cores = cores, household = T)
## 
## Association model
##  * Number of SNPs: 307984 
##  * Input format: genocov.files 
##  * Number of significal SNPs: 3 (Bonferroni correction with alpha 0.05)
##          SNP NAv      chi            pSNP      bSNP   bSNPse   Varexp
## 1:  rs710446 335 35.23666 0.0000000029198 -0.496124 0.083578 0.123276
## 2: rs4241824 335 33.93267 0.0000000057053 -0.485302 0.083311 0.095803
## 3: rs4253399 335 31.49100 0.0000000200370 -0.482461 0.085974 0.081138
##     est_maf  est_mac dosage_sd       pos chr
## 1: 0.547689 366.9516  0.689128 187942621   3
## 2: 0.470977 315.5543  0.710904 187428781   4
## 3: 0.585840 392.5128  0.714496 187425088   4
plot(A.F11)

plot(A.F11, "qq")

We observe that 3 significant SNPs are found. These results are in concordance with those previously reported on the FXI phenotype of the GAIT1 project (Sabater-Lleal et al. (2012)). There are three significant loci: rs710446 and rs4253399 located in the structural F11 gene, and rs4241824, located in the kininogen 1 (KNG1) gene. Both rs710446 and rs4241824 were reported in our previous GWAS published in (Sabater-Lleal et al. (2012)).

L.F11 <- solarMultipoint(tr_FXI ~ AGE, data = pdat, 
  mibdir = mibdir, 
  chr = 1:22, interval = 5, 
  cores = cores, verbose = 1)

The linkage model is described by L.F11.

summary(L.F11)
## 
## Call: solarMultipoint(formula = tr_FXI ~ AGE, data = dat, mibddir = mibddir, 
##     chr = 1:22, interval = 5, cores = cores, verbose = 1)
## 
## Multipoint model
##  * Number of used markers: 921 
##  * Number of passes: 1 
##  * Maximum LOD score: 1.79 
##   -- chr: 2 
##   -- position: 65 cM
plot(L.F11)