DBSLMM

Deterministic Bayesian Sparse Linear Mixed Model
There are two versions of DBSLMM: the tuning version and the deterministic version. The tuning version examines three different heritability choices and requires a validation data to tune the heritability hyper-parameter. The deterministic version uses one heritability estimate and directly fit the model in the training data without a separate validation data. Both versions requires a reference data to compute the SNP correlation matrix. In our experience, the tuning version may work more accurately than the deterministic version.

Update log

v0.3 Online Server

• provides the online version https://www.pgs-server.com/.

  v0.3

• fixes the bug of model fiting

  v0.21

• fits DBSLMM in different heritabiliies with one clumping
• uses a script to make the usage of DBSLMM-tuning version more easier.

  v0.2

• validates the flods of heritability: 0.8, 1 and 1.2
• fits the LMM, when the chromosome without any large effect SNPs
• fits the external validation all by R code.

Tutorial for DBSLMM (v0.3)

In this version, we use DBSLMM_script.sh to make the usage of DBSLMM more easier. v0.3 needs valg to be the whole genome plink file. By parameter -m, we give two different model assumptions, including DBSLMM and LMM. Specially, LMM model assumption only have the default version, because it do not need to tune -h2f.

PACK_DIR=/your/path/
SPLITCHR=${PACK_DIR}DBSLMM/software/SPLITCHR.R
PLINK=${PACK_DIR}plink_1.9/plink
DBSLMM=${PACK_DIR}DBSLMM/DBSLMM_script.sh

# Split into chromosome
DATADIR=/your/path/example_data/
summ=${DATADIR}all/summary
Rscript ${SPLITCHR} --summary ${summ}.assoc.txt

# Set parameters
BLOCK=${PACK_DIR}DBSLMM/LDblock/chr
herit=/your/path/herit.log
index=r2
thread=1
outpath=${DATADIR}output/

# DBSLMM tuning version (without covariates)
type=t
valg=${DATADIR}val/valid
valp=${DATADIR}val/valid_pheno.txt
model=DBSLMM
sh ${DBSLMM} -D ${PACK_DIR} -p ${PLINK} -B ${BLOCK} -s ${summ} -H ${herit} -m ${model} -G ${valg} -P ${valp}\
             -l ${col} -T ${type}  -i ${index} -t ${thread} -o ${outpath}

# DBSLMM automatic version (without covariates)
type=d
refp=${DATADIR}val/val
model=DBSLMM
sh ${DBSLMM} -D ${PACK_DIR} -p ${PLINK} -B ${BLOCK} -s ${summ} -H ${herit} -m ${model} -G ${refp}\
             -T ${type}  -i ${index} -t ${thread} -o ${outpath}

# LMM version
type=d
refp=${DATADIR}val/val
model=LMM
sh ${DBSLMM} -D ${PACK_DIR} -p ${PLINK} -B ${BLOCK} -s ${summ} -H ${herit} -m ${model} -G ${refp}\
             -T ${type}  -i ${index} -t ${thread} -o ${outpath}

If the user wants to change the fold of heritability, you can revise the setting in DBSLMM_script.sh. You should use the output file of ldsc as -H parameter of DBSLMM. The download link of dbslmm is https://drive.google.com/file/d/1eAbEyhF8rO_faOFL3jqRo9LmfgJNRH6K/view?usp=sharing.

Tutorial for external test only using summary statistics

Make SNP correlation matrix

We should use reference panel to construct SNP correlation matrix. You can treat 1000 Genome Project as reference panel. We also need the block information. The code is MAKELD.R.

mkld=/your/path/MAKELD.R
# construct SNP corrlation matrix for each chromosome
for chr in `seq 1 22`
do
bfile=/your/path/chr${chr}
blockfile=/your/path/chr${chr}.bed
plink=/your/path/plink-1.9
outpath=/your/path/outpath/
Rscript ${mkld} --bfile ${bfile} --blockfile ${blockfile} --plink ${plink} --outpath ${outpath} --chr ${chr}
done

Estimate R²

The format of extsumm is the same as that of LDSC.

SNP N Z A1 A2
rs1983865 253135 3.79310344827586 T C
rs1983864 251364 -4.51612903225806 T G
rs12411954 253213 0.413793103448276 T C
rs7077266 250092 -0.92 T G

We should use the standardized SNP effect size. You have two options. First, the variant ID is read from column 1, an allele code is read from the following column, the standardized effect size associated with the named allele is read from the column after the allele column. E.g.

esteff=/your/path/esteff.txt,1,2,3

Second, the variant ID is read from column 1, an allele code is read from the following column, the standardized effect size associated with the named allele is read from the column after the allele column, the MAF with the named allele is read from the last column. E.g.

esteff=/your/path/esteff.txt,1,2,3,4

The example of EXTERNAL.R is as following:

external=/your/path/EXTERNAL.R
extsumm=/your/path/extsumm.ldsc.gz
esteff=/your/path/esteff.txt,1,2,3
LDpath=/your/path/LDpath/
outpath=/your/path/outpath/
Rscript ${external} --extsumm ${extsumm} --esteff ${esteff} --LDpath ${LDpath} --outpath ${outpath}