Adjust Kinships

When estimating heritability using Haseman-Elston or PCGC Regression and including covariates, it is necessary to first produce adjusted kinship matrices, obtained by regressing the original kinship matrices on the covariates. This is because, whereas REML regresses the phenotype on the covariates and kinships jointly, HE and PCGC instead first adjusts the phenotype and kinships for the covariates, then regresses the adjusted phenotypes on the adjusted kinships (note that it is not necessary to separately adjust the phenotypes for the covariates, as LDAK does this automatically within the HE and PCGC routines).

The command for adjusting a kinship matrix is

--adjust-grm <output>

which requires the options

--grm <grmstem> - to provide a kinship matrix. Note that it is not possible to use --mgrm, so if wishing to adjust multiple kinship matrices, you should run --adjust-grm once for each.

--covar <covarfile> - provide covariates (in PLINK format).

If you will be estimating heritability using only a subset of samples, you should ideally use the same filtering now (i.e., add --keep to specify a list of samples or --pheno to consider only samples with non-missing phenotypes).

The adjusted kinship matrix will be saved with the stem <output>. Add --kinship-gz YES or --kinship-raw YES to save in alternative formats.
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Example: for this we use the file test.fam available in the Test Datasets and the kinship matrices in the folder partitions calculated in Get Kinships.

First we make a covariate file providing the sex of each individual (recorded in Column 5 of test.fam)

awk < test.fam '{print $1, $2, $5}' > sex.covar

Then we regress onto these each of the four kinship matrices

../ldak.out --adjust-grm partitions/kinships.1.sex --covar sex.covar --grm partitions/kinships.1
../ldak.out --adjust-grm partitions/kinships.2.sex --covar sex.covar --grm partitions/kinships.2
../ldak.out --adjust-grm partitions/kinships.3.sex --covar sex.covar --grm partitions/kinships.3
../ldak.out --adjust-grm partitions/kinships.all.sex --covar sex.covar --grm partitions/kinships.all