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Alcoholism and Our Genes
Scientific American
Current Issues in Biology
Volume 5
Lectures by Greg Podgorski, Utah State University
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Twin and adoption studies show that genetics account
for about 50% of an individual’s risk of alcoholism.
• Alcoholism is genetically complex: multiple genes
interact with one another and with the environment to
affect the risk of alcohol dependence.
• Distinguishing genetic and environmental influences
is challenging.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Variants of any particular gene contribute modestly to
the risk of alcoholism, increasing risk no more than 20%
to 40%.
• Genes influence alcoholism risk by affecting
physiological processes that in turn respond to an
individual’s experiences.
• Understanding the genes and physiological processes
that contribute to alcohol dependency will improve
prevention and treatment strategies.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Dependency on any substance occurs when an
individual shows at least three of the following
symptoms over a year or more:
tolerance for large doses of the substance
 withdrawal reactions
 loss of control over the substance’s use
 efforts to stop or cut down use of the substance
 a great deal of time spent on use of the substance
 giving up other activities to use the substance
 continued substance use despite physical and
psychological problems

Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Endophenotypes are more useful than behavioral
traits in the search for alcoholism risk genes.
• An endophenotype is a biochemical or physiological
trait.
• Endophenotypes often reflect the effects of individual
genes more directly than complex behavioral traits.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Endophenotypes useful in probing the effects of
alcoholism risk genes include
• Enzyme activity
• Levels and types of receptor molecules,
• Brain activity (measured using
electroencephalograms, or EEGs).
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• EEGs differ characteristically in the brains of
alcoholics and non-alcoholics.
• EEGs can distinguish
between the firing of
excitatory and inhibitory
neurons in brain regions
that control behaviors.
• Imbalances between
excitation and inhibition can
produce impulsivity, depression, anxiety, and
susceptibility to substance abuse, including alcohol.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• The brains of many alcoholics show an imbalance in
favor of excitatory neuron activity over inhibitory
neuron activity.
• This imbalance is known as disinhibition.
• Disinhibition reflects a decrease in inhibitory neuron
activity in brain regions responsible for judgment and
decision-making.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Disinhibition appears to be heritable, as it is seen
frequently in the children of alcoholics.
• The observation of a heritable endophenotype
associated with alcoholism spurred the search for
genetic risk factors.
• So far, these studies have uncovered roughly one
dozen gene variants that influence the risk of
alcoholism.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• The Collaborative Study on the Genetics of Alcoholism
(COGA) identified families deeply affected by
alcoholism.
• Alcoholics and family members
provided DNA samples and
personal information relevant
to alcoholism.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• It is important to understand that there are no genes
that “cause” alcoholism.
• Instead, there are naturally occurring variants of
genes.
• Some variants reduce the risk of alcoholism, while
others increase it.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
Mapping Alcoholism-Associated Gene Variants
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
Alcohol is broken down in the following way:
alcohol
dehydrogenase
alcohol
(ethanol)
acetaldehyde
reductase
acetaldehyde
acetic acid
• Alcohol and acetaldehyde are toxic.
• Acetic acid is used by cells for energy.
• Alcohol dehydrogenase and acetaldehyde reductase
are enzymes that catalyze the reactions.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
alcohol
dehydrogenase
alcohol
(ethanol)
acetaldehyde
acetaldehyde
reductase
acetic acid
• The first known genetic variant influencing the risk of
alcoholism was discovered in the aldehyde
dehydrogenase gene, ALDH1.
• An ALDH1 variant common in East Asian populations
produces an alcohol dehydrogenase enzyme with
reduced activity.
• Individuals who carry this variant accumulate high
levels of acetaldehyde after drinking.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Acetaldehyde produces symptoms that include hot,
flushed skin, heart palpitations, dizziness, and
weakness.
• For these reasons, people with the ALDH1 gene
variant experience less pleasure while drinking.
• Therefore, the ALDH1 gene variant protects against
alcoholism.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
alcohol
dehydrogenase
alcohol
(ethanol)
acetaldehyde
acetaldehyde
reductase
acetic acid
• A group of genes (ADHs) produces the enzyme
alcohol dehydrogenase.
• Variants in the ADH1 and ADH4 genes increase the
risk of alcoholism.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Brain neurotransmitters are molecules released by
one neuron that control the activity of another neuron.
• Neurotransmitters bind to receptor molecules on the
surface of responsive cells.
• Variants in genes that influence neurotransmitter
receptors influence susceptibility to alcoholism.
• The receptors important in alcoholism control
excitation or inhibition of the brain’s decision-making
centers.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• The GABRA2 gene produces a receptor for a
neurotransmitter that inhibits the activation of neurons.
• A GABRA2 gene variant that reduces the amount of
receptor leads to disinhibition by tipping the balance
of brain activity to overstimulation.
• This GABRA2 gene variant is a genetic risk factor in
alcoholism and impulsivity.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• The CHRM2 gene produces a receptor for a
neurotransmitter that excites neurons.
• A CHRM2 gene variant that reduces the amount of
receptor weakens brain activity involved in decision
making.
• This CHRM2 gene variant is a genetic risk factor in
alcoholism and depression.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• Gene variants that influence the
risk of alcoholism also affect
behavior in children:
• GABRA2 risk-associated
variants increase the incidence
of conduct disorders.
• CHRM2 risk-associated
variants increase the incidence
of depression.
• These findings show there are different pathways
and physiological mechanisms to alcoholism.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Concept Review
• As more alcoholism-associated genes are discovered,
they will be used to determine who is at risk and how
to tailor treatments to help those with alcohol
problems.
• Findings about alcoholism-associated genes may help
in the prevention and treatment of other types of
substance abuse.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
Genetic factors contribute about _____ to an individual’s
risk of alcoholism.
a) 5%
b) 20%
c) 50%
d) 90%
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
Genetic factors contribute about _____ to an individual’s
risk of alcoholism.
c) 50%
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
Disorders caused by multiple genes that interact with
each other and with an individual’s environment are:
a) Mendelian diseases.
b) genetically complex disorders.
c) endophenotypes.
d) disinhibition disorders.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
Disorders caused by multiple genes that interact with
each other and with an individual’s environment are:
b) genetically complex disorders.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
Endophenotypes are useful in searches for alcoholismassociated gene variants because they:
a) reflect gene activity more directly than behavioral
phenotypes.
b) are internal rather than external phenotypes.
c) are the DNA sequences that cause alcoholism.
d) exist on the same chromosomes as alcoholismassociated gene variants.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
Endophenotypes are useful in searches for alcoholismassociated gene variants because they:
a) reflect gene activity more directly than behavioral
phenotypes.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
In the brain’s decision-making centers, alcoholics often
show:
a) no nerve cell activity.
b) nerve cells that are active only when alcohol levels
are high.
c) a shift in the balance of inhibitory and excitatory inputs
in favor of excitation.
d) a shift in the balance of inhibitory and excitatory inputs
in favor of inhibition.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
In the brain’s decision-making centers, alcoholics often
show:
c) a shift in the balance of inhibitory and excitatory inputs
in favor of excitation.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
One gene variant that protects against alcoholism does
so by producing:
a) a low-activity form of aldehyde dehydrogenase.
b) a high-activity form of alcohol dehydrogenase.
c) low levels of a receptor (GABA2) that inhibits
neurons.
d) high levels of a receptor (CHRM2) that leads to
depression.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Testing Your Comprehension
One gene variant that protects against alcoholism does
so by producing:
a) a low-activity form of aldehyde dehydrogenase.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Biology and Society
Since genetic factors play such a large role in
alcoholism, alcoholics cannot be held accountable for
their drinking.
Strongly
Disagree
A
B
C
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
D
E
Strongly
Agree
Alcoholism and Our Genes
Thinking About Science
The CHRM2 gene produces a receptor for a stimulatory
neurotransmitter. Some CHRM2 gene variants increase
the risk of alcoholism. Which of the following is a
plausible hypothesis for how CHRM2 variants increase
the risk of alcoholism?
a) They produce receptors that cannot bind to the
neurotransmitter.
b) They produce half the normal amount of receptor.
c) They produce receptors that are activated at unusually
low levels of neurotransmitter.
d) They produce unstable receptors that are rapidly
degraded.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Thinking About Science
The CHRM2 gene produces a receptor for a stimulatory
neurotransmitter and some CHRM2 gene variants
increase the risk of alcoholism. Which of the following is a
plausible hypothesis for how CHRM2 variants increase
the risk of alcoholism?
c) They produce receptors that are activated at unusually
low levels of neurotransmitter.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Interpreting Charts and Graphs
Which
of the
following
conclusions
is supported
by the graph?
a) Children of alcoholics are at risk of becoming
alcoholics as adults.
b) Alcoholism is caused by an altered response to
stimulation.
c) Alcoholics show a delayed response to stimulation.
d) Alcoholics show a reduced response to stimulation.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings
Alcoholism and Our Genes
Interpreting Charts and Graphs
Which
of the
following
conclusions
is supported
by the graph?
d) Alcoholics show a reduced response to stimulation.
Copyright © 2009 Pearson Education, Inc. publishing as Benjamin Cummings