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Lecture 10

PSYT 301 Lecture Notes - Lecture 10: Peripheral Artery Disease, Decode Genetics, Nicotine


Department
Psychiatry
Course Code
PSYT 301
Professor
Kathryn Gill
Lecture
10

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Lecture 11: Nicotine Wrap-up
Why do people start smoking and why is it difficult to quit?
Genetic factors:
- current candidate genes under investigation: polymorphisms of DAT, 5HT, dopamine,
as well as CYP450 enzymes
- might be genetic factors that influence why people cannot quit, or who smokes more
than others
- DeCode Genetics - Nature, April 2008: A variant associated with nicotine
dependence, lung cancer, and peripheral arterial disease
- a common variant in the nAChR on chromosome 15q24 was associated with
smoking quantity tobacco dependence and the risk of lung cancer and arterial
disease
- however the results on chromosome 15 were not completely replicated in
subsequent studies
- now, genetic mapping is focusing on the enzymes involved in nicotine
metabolism
- reproducibility is the ability of an entire experiment or study to be duplicated,
main principles of the scientific method, if more people confirm that it can be
replicated with the same results, adds “truth” to the claim
- influenced by small sample, or certain genetic factors might be
segregated in one population but not another, the findings in one
population is not conclusive for a total population
- read links on mycourses about reproducibility
- half of psychology studies fais reproducibility test, only 39 of the 100
major studies were found to not be replicated
- Culverhouse 2014: Multiple distinct beta3-alpha6 variants are genetic risk factors for
nicotine dependence in African Americans and European Americans
- large sample size (>5000)
- looking for if the genetic variants for one drug dependence is specific to that
drug, or to multiple different drugs
- diverse sampling
- the region of chromosome 8p11 that include alpha6 and beta3 nicotinic
receptor subunit gene cluster has been associated with smoking behaviour (#
of cigarettes smoked per day)
- variants do not appear to be associated with other drugs
- Fagerstrom Nicotine Dependence Test, 5 questions, higher the score the
more nicotine dependent someone is
- how long after waking up do you light the first cigarette?
- difficult to abstain?
- which cigarette would you find the hardest to give up?
- how many cigarettes do you smoke in a day?
- do you smoke more in the morning that in the rest of the day?
- nicotine dependence and alcohol dependence were most often comorbid
- alpha 3, 4, 5, beta 4,6 -- review found that multiple different genes
- human genetic disorders and traits are complex, involving multiple genes and gene-
environment interactions, genetic heterogeneity with likely polygenic influences, intra-familial
major gene effects, incomplete penetrance, gender differences, manifestations of phenotype
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