How to estimate disease heritability from RNA-seq data?

Question

[iman.sadeghi]

Hi,

I want to estimate heritability from gene expression data for diseases. I found heritseq R package, however it measures heritability of genes (not diseases). Anybody knows if it is possible, if so, how?

Answer 1

[GouthamAtla]

You are mixing concepts here.

Heritability is proportion of phenotypic variation explained by genetics. The 'phenotype' could be gene expression, or a 'disease' or something else where you have measured a phenotype and have genotypes. To estimate the 'disease' heritability, you need GWAS summary statistics where you have 'disease status' of hundreds of thousands of individuals and their genotypes, so you try to explain how much of the disease can be explained by genotypes.

Now you are asking, you want to estimate disease heritability by gene-expression which doesn't make sense because 'heritability' by definition is contribution of genetics to phenotype.

You can select genetic variants that overlap genomic regions of certain genes of your interest (or QTLs for those genes) and try to estimate heritability of a disease using summary statistics from GWAS data. If you could explain a part of heritabilty of the disease just by using subset of variants, then the genes of your interest might have some relevance to the disease.