Introduction

Figure 1

Single gene disorder
Single-gene diseases like cystic fibrosis are relatively well understood. In cystic fibrosis, mutations in the coding region of the CFTR gene result in a defective protein, leading to excess mucus production that can damage the lungs and digestive system.

Figure 2

Figures showing GWAS Catalog
GWAS variants such as SNPs are often in non-coding regions of the genome, indicating that they regulate gene expression.

Figure 3

Figure showing regulation of gene by SNP
Here a non-coding SNP influences expression of a gene, which in turn affects a disease phenotype or other outcome of interest.

Figure 4

Figure showing SNP regulating gene which affects disease
Genetic variants like SNPs often affect gene expression locally near the gene that they regulate (in cis).

Figure 5

Figure showing trans regulation
Alternatively, SNPs often affect gene expression distally from the gene that they regulate (in trans), often from a different chromosome altogether.

Genetic Drivers of Pancreatic Islet Function

Figure 1

LOD plot for insulin area under the curve
LOD plot for insulin area under the curve

Load and explore the data

Review Mapping Steps

Mapping A Single Gene Expression Trait

Mapping Many Gene Expression Traits

Creating A Transcriptome Map

Transcriptome Map of cis and trans eQTL

Maximum eQTL Peaks and Nearby Genes

Figure 1

LOD plot for gene Hnf1b.
LOD plot for gene Hnf1b.

Figure 2

SNP association plot for gene Hnf1b.
SNP association plot for gene Hnf1b.

Interpreting qtl2 results

Figure 1

Attie et al, 2018 Supplementary Figure S7 ::::::::::::::::::::::::::::::::::::: challenge

Mediation Analysis

Figure 1

In complete mediation an independent (predictor) variable influences the dependent (response) variable indirectly through a mediator variable. Mediation analysis is widely used in the social sciences including psychology. In biomedicine, mediation analysis has been employed to investigate how gene expression mediates the effects of genetic variants on complex phenotypes and disease.

Figure 2

A non-coding SNP affects expression of gene 1 in cis. Gene 1 mediates expression of gene 2. Instead of the expression of one gene impacting another, expression of gene 1 in the graphic above could impact a physiological phenotype like blood glucose. Expression of gene 1 would mediate the relationship between the non-coding SNP and the glucose phenotype.

Figure 3

Chromosome 13 gene Akr1e1 is affected by expression in both cis and trans by genes on chromosomes 13 and 4. Myo15b is located on chromosome 11. How would you interpret the following LOD plot? On which chromosome(s) would you expect to find the driver gene(s)? The SNP(s)?

Figure 4

Chromosome 11 gene Myo15b is affected by expression of a trans gene in the chromosome 2 hotspot. The QTL Viewer for the Attie islet data integrates mediation into exploration of the data. Below, mediation analysis identifies gene Hnf4a as the chromosome 2 gene that impacts Myo15b expression.

Figure 5

Mediating expression of Myo15b identifies Hnf4a as the gene that drops the LOD score from greater than 70 to less than 50.
Mediating expression of Myo15b identifies Hnf4a as the gene that drops the LOD score from greater than 70 to less than 50.