Behavioral Genetics Topic - PowerPoint PPT Presentation

Loading...

PPT – Behavioral Genetics Topic PowerPoint presentation | free to view - id: 24b35e-ZjNmY



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Behavioral Genetics Topic

Description:

Association of ALDH2 Deficiency with NOT using Substances in Past Year at Follow-up ... and research designs to study the nature and origins of individual differences ... – PowerPoint PPT presentation

Number of Views:124
Avg rating:3.0/5.0
Slides: 25
Provided by: mattm2
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Behavioral Genetics Topic


1
Behavioral Genetics Topic 13
  • Human Alcohol Abuse and Alcoholism - ALDH

2
Some Basic Epidemiology
  • Alcoholism is very common, with rates much higher
    in men than women
  • Alcoholism rates vary markedly across cultures
  • Alcoholism is heritable, especially in males
  • Major risk factors include
  • Ethnicity
  • Other psychiatric disorders
  • Early initiation
  • Positive family history
  • Other, especially externalizing, psychopathology
  • Disinhibited personality traits

3
Flushing Response
  • Dysphoric effects that occur w/i 15 minutes of
    drinking
  • Heart palpitation
  • Facial reddening
  • Nausea, dizziness
  • There are large ethnic group differences in rate
    of flushing metabolic not cultural

4
Inherited ALDH2 Deficiency
NAD
NAD
Alcohol
Acetaldehyde
Acetate
ALDH2 Mutation
ADH
ALDH
5
ALDH2 Deficiency
  • Mutation (ALDH22 v wild-type ALDH21) is a
    single nucleotide change in exon 12 that results
    in a glu/lys exchange in position 487
  • Deficient form of the enzyme carried by approx
    50 of Northern East Asians but only 2 of
    alcoholics from those regions

6
ALDH2 Deficiency Among Japanese
Alcoholics (Higuchi et al. 1994)
Heterozygote Frequency
7
Asian-American Adopted Youth
8
Is ALDH Deficiency Protective in Adopted Youth?
p .39
p .04
p .02
Irons et al. (2007)
9
Do Environmental Factors Diminish ALDH Effect?
  • ParAlc Adoptive parent DSM Sx of Alcohol
    Dependence
  • ParTol Perceived adoptive parent tolerance for
    adolescent substance use
  • SibAlc Sibling alcohol use at initial
    assessment
  • SibTol Perceived sibling tolerance for
    adolescent substance use

10
Sibling Factors DO Appear to Diminish ALDH Effect
p .24
p .69
p .01
p .04
Irons et al. (2006)
11
Gateway Model
Other Drug Use
Delinquency
Adolescent Alcohol
Adolescent Tobacco
Bad Peer Models
12
Will Reducing Adolescent Drinking Reduce Other
Adolescent Problems?
Experimental Approach
?
Intervention
Reduced Drinking
Reduced Disinhibition
Population
Control
No Effect
No Effect
Mendelian Randomization
Reduced Disinhibition
?
ALDH -
Reduced Drinking
Population
ALDH
No Effect
No Effect
13
Intake Disinhibition in Adolescents With and
Without ALDH2 Deficiency
14
Association of ALDH2 Deficiency with NOT using
Substances in Past Year at Follow-up
15
ALDH and Adolescent Drinking
  • Is protective ALDH deficiency associated with
    lower rates of being drunk
  • Is NOT deterministic Rearing environment can
    diminish ALDH protective effects
  • Source of environmental effect Siblings are an
    important but perhaps underappreciated factor
  • Mendelian Randomization Drinking interventions
    may reduce drinking and drinking-related
    problems. Their effect on other indicators of
    disinhibitory psychopathology or adolescent
    substance use are less clear.

16
Topic 14 Conclusion
  • Definition
  • Behavioral genetics - that area of psychology
    that is concerned with the application of genetic
    methods and research designs to study the nature
    and origins of individual differences in human
    and animal behavior.

17
Methodologies
  • Mendelian (single-gene) inheritance
  • PKU, Huntingtons, CAH
  • Chromosomal anomalies/Structural Variation
  • Down Syndrome, Williams Syndrome, VCFS
  • Twin/Adoption Studies
  • Complementary methodologies
  • Biometric Analysis
  • Variance component estimation
  • Gene Identification in Humans
  • Linkage, Association, Linkage Disequilibrium
  • Animal Methods
  • Selection, Inbred Strains, Forward Genetics (QTL,
    mutagenesis, microarray), Reverse Genetic
    (transgenics, knock-outs)

18
Nature of Genetic Influence
  • Heritability
  • Virtually all behavioral traits are in part
    heritable
  • Common heritable factors may account for
    correlations among disorders
  • Heritability estimates are approximations
  • Heritability is neither an index of immutability
    nor an explanation of behavior

19
Nature of Genetic Influence
  • Genes and the Human Genome Project
  • 20,000 to 25,000 genes and 11,000,000 SNPs, and
    large amount of structural variation (e.g., CNVs)
  • Gene identification has been difficult
  • Mendelian vs. oligogenic vs. polygenic
  • Positional cloning strategy has produced few
    successes
  • But there are some leads (5-HTT, DAT1, DRD4,
    ALDH2, GABRA2, COMT)
  • Prospects for the Future
  • Large-scale LD studies in humans (500,000 SNPs)
  • Focus on regulatory as well as structural (i.e.,
    coding) variability
  • Animal models based on homology synteny

20
Benefits of finding genes for human behavior?
  • Better understanding of the nature and origins of
    behavior
  • Pharmacological interventions based on genotype
    (the 5-HTT example)
  • Targeted early prevention (e.g., treating
    unaffected siblings of schizophrenics)

21
Merikangas, K.R. Risch, N. (2003). Genomic
priorities and public health. Science, 302
599-601.
22
Nature of Environmental Influence
  • Familial resemblance is potentially a function of
    both shared genes and shared environment
  • Have we overestimated the impact of parents?
  • Shared vs. non-shared environmental effects
  • Changing balance across development for some
    traits
  • SZ, BP, Depression, ADHD
  • Gene-environment interplay
  • GxE and the diathesis-stress model
  • PKU
  • MAO-A and aggression
  • 5HTTLPR and depression
  • G-E correlation
  • Ge et al. adoption study
  • Epigenesis

23
Principled Critiques of BG
  • For psychologists, as well as for medical
    researchers, the purpose of identifying
    undesirable predispositions of individuals should
    be to devise more effective health-promoting
    interventions, not to discourage such attempts on
    the supposition that these predispositions are
    genetically based and therefore intractable.
  • D. Baumrind (1993)

24
Final Admonitions
  • Dont believe it unless it is replicable
  • Single studies are not definitive, require a
    coherent pattern of results
  • Study for the final attend review session on
    Friday 14 December 100 PM in N227 Elliott Hall
  • Arrive for the final on time (800 AM, Monday 17
    December in N119 Elliott Hall), and
About PowerShow.com