Jmp genomics

Genomic heritability represents the proportion of genetic variance explained by SNPs in the phenotypic variance. The estimated genetic influence on the traits was based on the SNP data matrix [35 (link)]. The measured SNP-level variation was used to estimate the genetic similarity between individuals, and this estimated genetic similarity was compared to phenotypic similarity to produce a heritability estimate. To estimate the heritability of the fetal weight, sex was included as fixed effect, the genetic similarity matrix between individuals was first computed as identity-by-descent of each pair for the k-matrix (SNPs) used as the random effect.
Fetal weight was analysed for an association with SNPs using a mixed-model analysis of variance in JMP Genomics (SAS Institute, Cary, NC, USA). Mixed-model analysis tests an association between traits and a single SNPs and simultaneously adjusts for population structure and family relatedness [13 (link)] which was considered here based on the genetic similarity matrix estimated as a k-matrix. This genome-wide relatedness was used as random effects. For control of population stratification, top principal components (PC) which explain variation of more than 1% were considered as covariates. In total, 18 PCs were included as covariates. Additionally, genotype and sex were used as fixed effects.

Power analysis was performed using the mixed model power expression utility in JMP Genomics (SAS Institute, Cary, NC, USA). We created a design file with duplicates of 10 guide RNAs and designated one guide as the causal variant. Additional random effect options for representing batch effects (distributing the guides across into two batches of 5) and clone effects (where the causal variant was represented by two different clones) allowed modeling of the impact of these additional sources of variance. We assessed power at α = 0.05, 0.01, and 0.001 for effect sizes of the causal variant in increments of 0.1 standard deviation units (sdu) between 0 and 2, assuming experiments with 2, 4, 8, or 16 replicates of each guide. Batch and clone effects were assumed to be 0.1 or 0.2 sdu. For additional analysis, three of the guides were assumed to affect gene expression, modeling the situation where multiple linked variants account for an eQTL effect.