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Brendan Burke and Kyle Steffen
Important New Tool in Genomic
Medicine
 GWAS is used to estimate disease risk and test SNPs(
the most common type of genetic variation among
people) for association to hundred, even thousands of
people.
 It identifies a correlation between a genetic change in
heredity and the incidence of a complex disease.
 GWAS has increased our understanding of the
pathophysiology of complex disease.
General Procedure
 Gather a group of people to be tested for the SNPs that you want
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to test.
As an example, in one the studies, they studied 2500 that had
people that had Type 2 Diabetes and 2500 people who did not (as
their control). The researchers then scanned their genomes to
see which SNPs are present.
They found that people with Type 2 Diabetes have a unique set of
SNPs in common and they located the QTLs( Quantitative Trait
Loci) of those SNPs. They located the QTL of the SNPs
Then the researchers went to the QTL to see on the human
genome map to see which genes are there.
They then attempted to link those unique SNPs to a known gene
function.
Common Disease-Common Variant
Hypothesis
 This hypothesis predicts that disease-causing alleles
will be found in all human populations which manifest
a given disease.
 Common variants are known to exist in coding and
regulatory sequences of genes.
 Single nucleotide polymorphisms are valuable
genomic signposts in the search for common variants
that influence susceptibility to common diseases.
 Common SNPs have been linked to diseases such as
type 2 diabetes, Alzheimer’s, schizophrenia, and
hypertension.
GWAS Results
 GWAS has over 1700 publications of their work
 GWAS only publishes results that attempt to assay
at least 100,000 SNPs.
 Their publications are organized by date, most
recent to least, and studies focusing only on
candidate genes are excluded.
 Their publications include over 250 human traits
and diseases.
 Also, there are over 7291 SNP-trait associations.
Current GWAS Studies
 Studies with Type 2 diabetes
 Before the GWAS studies, only two loci were identified.
 Now due to the GWAS studies, forty-four loci have been
identified.
 The loci are also known to connect with glucose
metabolism pathways
Current GWAS Studies continued
 GWAS in Autoimmune Disease
 If a person has an autoimmune disease the immune
system mistakenly attacks itself, targeting the cells,
tissues, and organs of a person’s own body.
 Examples of Autoimmune diseases are Lupus, Multiple
Sclerosis, and Rheumatoid Arthritis.
 Before GWAS Studies, the genetic risk variants for
autoimmune disease was only 15.
 Now, because of the GWAS Studies, the risk variants has
been increased to 68.
GWAS Studies in Immune System
Genes
 Due to the GWAS Studies with the Immune Systems,
113 SNPs have been located.
 13 new regions have been discovered within the
immune systems and most of these systems have genes
with immune functions.
GWAS Studies in Inflammatory
Bowel Disease
 The main forms of inflammatory bowel disease are
Crohn’s disease and ulcerative colitis.
 Inflammatory bowel diseases are considered
autoimmune diseases, when the immune system
attacks the digestive system.
 The main difference between Crohn’s disease and
ulcerative colitis is the location and nature of the
inflammatory changes.
 Inflammatory bowel disease is caused by concentrated
milk fats, often found in processed foods.
GIANT Studies
 GIANT consortium is an international collaboration
that seeks to identify genetic loci that modulate
human body size and shape.
 GIANT consortium is a collaboration of different
groups, and their results represent their combined
efforts.
 Traits that have been studied are BMI, height, and
waist circumference.
 So far in their work, GIANT consortium have
identified common genetic variants at hundreds of loci
that are associated with anthropometric traits.
Malaria Resistance Medication
SNPs
 Spontaneous mutations within SNPs would give an
anti-malarial medication a reduced level of sensitivity.
This can be caused by a single point mutation or
multiple mutation
 The resistance to anti-malarials may be increased by a
process found in which a degree of phenotypic
plasticity( the ability of an organism with a given
genotype to change its phenotype in response to
changes in the environment) was seen which allows
the rapid development of resistance to a new drug,
even if the drug has not been previously experienced.
Blood Lipids
 Blood lipids(such as cholesterol and triglycerides) are
major risk factors found in patients that have heart
disease.
 Specific SNPs indicate that one does have heart disease.
 Due to GWAS Studies, there are now 95 known SNPs
that were associated with heart disease.
 Before GWAS Studies, only 59 SNPs were associated
with heart disease.
SNPs and IQ
 GWAS has explained that half the variation in I.Q. is
due to the variation in genes.
 Most of the genetic variation that is in this trait is due
to numerous genes of little effect.
 You inherit variants of these gens from both of your
parents, and your own trait value is to a large extent
both of your parents values.
 This issue is not arguing whether intelligence is
heritable, but how much you get from each of your
parents.
SNPs and Human Personality Traits
 Studies have shown that there are no SNPs associated
with any of the following personalities; Neuroticism,
Extraversion, Openness, Agreeableness and
Conscientiousness.
 The genes that we inherit have no direct or indirect
influence on our personalities.
 Although there have been some tests on twins showing
that genes do affect personalities, scientists have
concluded it’s the environment they grow up in.
SNPs and Human Personality Traits
 There are five identified independent genetic loci
associated with different facial phenotypes; PRDM16,
PAX3, TP63, C5orf50, and COL17A1.
 Three of these are involved in facial developments and
diseases.
 The other two are basically in charge of the facial
developments.
 This study may allow us to predict facial shape and
details in the future.
Questions
 What does GWAS stand for?
 What does QTL stand for?
 How many risk variants have been identified
for Autoimmune disease because of GWAS?
 What are two example of Autoimmune
diseases?
 What is the overall purpose of GWAS?
Bibliography
 www.genome.gov/gwastudies/
 www.genome.gov
 www.ncbi.nlm.nih.gov
 www.ncbi.nlm.nhi.gov/pubmed/23017373
 www.biomedcentral.com/1471-2350/8/s1/s17
 www.broadinstitute.org/news/2898
 www.ncbi.nlm.nih.gov/pmc/articles/pmc2574810/
THANK YOU
THE END