Thermo ebook on eQTL - 26

ing using the IGV interface around the region of
chr11:75487,056-75,647,783, we can see that there
are six GWAS results that map to the SERPINH1 gene
(Figure 7A). In addition, looking at eQTLs in whole
blood and breast mammary tissue tracks, we see
there are two SNPs that are eQTLs for the SERPINH1
gene. Note that these two eQTLs do not appear to
affect expression in whole blood. Entering SERPINH1
into the GTEx locus query box and filtering for whole
blood and breast tissue, we find there are indeed
two eQTLs for this gene in breast mammary tissue
(Figure 7B). Clicking on each of the two bars brings
up violin plots, showing the effect of different genotypes on the expression: one of them increases expression relative to the reference, and two decrease
expression (Figure 7C).

Conclusions
GWAS have provided extraordinarily useful information on the association between genotypes and phenotypes or pathologies. Although SNPs that fall within coding regions of genes provide clear avenues for
further investigations, the role of SNPs falling outside
of coding regions have been less obvious. The ability
of eQTLs to influence gene expression is significant
for understanding how these SNPs might contribute
to phenotypes. Combining the GTEx database queries
with TaqMan Assay verification is an easy way to solidify these links. Since the vast fraction of SNPs identified in GWAS fall outside of protein-coding regions,
the analysis of eQTLs in the context of GWAS provides
many opportunities to advance our understanding of
the genotype-phenotype association.

A literature search suggests that changes in
SERPINH1 (also known as HSP47) can influence cancer progression by increasing extracellular matrix
deposition.8 Thermo Fisher Scientific has TaqMan Assays available for SERPINH1 gene expression and for
the two SNPs that are eQTLs for this gene in breast
mammary tissue (Figure 7D). A custom TaqMan SNP
Genotyping Assay can be designed and ordered for
any SNP that might not be in the TaqMan collection.

The GTEx project was supported by the Common
Fund of the Office of the Director of the National
Institutes of Health (NIH) and by National Cancer
Institute (NCI); National Human Genome Research
Institute (NHGRI); National Heart, Lung, and Blood
Institute (NHLBI); National Institute on Drug Abuse
(NIDA); National Institute of Mental Health (NIMH);
and National Institute of Neurological Disorders and
Stroke (NINDS).

Thus, an investigator might use these reagents to
analyze more samples to reinforce the link between
these genotypes and SERPINH1 expression in breast
cancer. The investigator could use the SNP assays
to identify individuals that might be more at risk
because they have a genotype resulting in higher
SERPINH1 expression. Studies could be developed
to determine whether modulating SERPINH1 expression reduces the pathology of breast cancer samples. Thus, using these tools together may provide
insights into how genotypic variation driving gene
expression differences can influence pathologies.

References

Visscher PM et al. (2017) 10 years of GWAS discovery:
biology, function and translation. Am J Hum Genet
101:5-22.

Pal LR et al. (2015) Insights from GWAS: emerging
landscape of mechanisms underlying complex trait loci.
BMC Genomics 16 Suppl 8:S4.

MacArthur J et al. (2017) The new NHGRI-EBI catalog
of published genome-wide association studies (GWAS
Catalog). Nucleic Acids Res 45:D896-D901.

Thermo ebook on eQTL

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