inst/markdown/methods/germline_heritability.md

In CRI-iAtlas/iatlas-app: What the Package Does (One Line, Title Case)

Title: Heritability

Descriptions: We performed heritability analysis on 139 traits using a mixed-model approach implemented in genome-wide complex trait analysis (GCTA) genomic-relatedness-based restricted maximum-likelihood (GREML) method (Yang et al., 2010, 2011) to calculate the proportion of immune trait variation that is attributable to common genetic variants (Zaitlen and Kraft, 2012). Heritability analyses were conducted separately within each ancestry subgroup (NEuropean=7,813, NAfrican=863, NAsian=570, and NAmerican=209 individuals), which were derived from ancestry analysis.

To reduce bias in the heritability estimates, we removed one of each pair of related individuals with Ajk > 0.05 (calculated from SNPs with MAF > 0.01) prior to running GREML. We calculated heritability using an unconstrained approach (allowing heritability to be < 0 - those values were truncated in CRI iAtlas). We used the likelihood ratio test (LRT) implemented in GREML to test if heritability is different than zero for each of the immune traits analyzed and used Benjamini-Hochberg adjustment (Benjamini and Hochberg, 1995) to calculate the FDR. All heritability analyses were run with age, tumor type, sex and PC 1-7 as covariates.

We also used GREML to determine whether there are any contextual factors that interact with genome-wide common variant effects, including the major immune subtypes as determined by Thorsson et al and somatic mutations (divided into tertiles and dichotomized at 10 MB). We implemented the gene x environment (GxE) feature calculation in the European in GREML. For those immune traits for which we found nominally significant (p < 0.05) interactions, we calculated heritability in each stratified subset, as well as with immune subtype as an additional covariate. For GxE calculations, the LRT tests the significance of the variance of GxE interaction effects.

Reference Listing

Contributors: Rosalyn Sayaman, Elad Ziv

CRI-iAtlas/iatlas-app documentation built on Feb. 7, 2025, 9:02 p.m.