Behavioral Genetics

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Behavioral Genetics

• Jeffrey Clothier, M.D.

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Objectives

• Describe the genetic methods applied to behavior
• Describe role of genetics and environment in
  conditions such as MR, IQ, Substance abuse,
  schizophrenia, affective disorders, and dementing
  illnesses
• Describe the value of twin studies and adoption
  studies in behavioral genetic studies
• Define heritability

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Methods of Genetic investigations

• Transmission studies
• Family
• Twin
• Adoption
• Pedigree analysis and linkage studies
• Pedigree and genetic markers
• Molecular studies
• Point is to try and predict who will get sick

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Family studies

• Describe risk of occurrence of disease in two
  related at risk persons
• concordance rate is related to shared
  characteristics
• genetic and environmental
• Heritability -A measure of the relative influence
  of genetics to overall family transmission

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Twin studies

• rare but precious resource for understanding
  genetic influences
• Monozygote twins are 100 genetic and 100
  environmental ideally
• Dizygote twins are 50 genetic and 100
  environmental ideally
• Difference b/w DZ and MZ concordance rates is a
  measure of genetic influence

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Adoption studies-control environmental factors

• Adoptees family method(index case is the child)
• calculates concordance in parents of index case
• needs information about adoptive and biologic
  parents
• greater risk in biologic parents than adoptive
  parents suggest genetic factors

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Adoption studies (cont)

• Adoptees study method (index case is the parent)
• calculates risk to children of index case
• increased risk to adopted away children of index
  case over adopted children of controls suggest
  genetic factors
• Crossfostering method
• Compares risk to adoptees whose biologic parents
  were ill and adoptive parents were normal with
  adoptees whose biologic parents were normal and
  adoptive parents were ill.

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cross fostering method
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Problems with twin studies

• Ascertainment-diagnostic criteria
• adequacy of control
• phenotypic classification
• determination of zygosity

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Pedigree analysis

• address questions of penetrance and transmission
  mechanisms
• single major locus
• multifactorial-polygenetic
• phenotype vs. genotype
• effect of variable penetrance
• assumption of dominance
• endophenotypic expression

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Single major locus transmission

• Autosomal
• recessive
• Wilsons disease (ceruloplasmin and copper)
• damage to liver, cornea and basal ganglia
• Phenylketonuria (phenylalanine hydroxylase)
• build up of abnormal metabolite (phenylpyruvic
  acid
• carrier state is common (1 in 50)
• endophenotypic expression

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Single major locus (cont)

• Autosomal dominant
• Huntingtons disease (atrophy of the caudate
  nucleus)
• chorea and mental disorders
• appears around mid 30s
• Chromosome 4

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Single Major locus (cont)

• Sex linked disorders
• Usually x linked recessive (exLesch-Nyhan
  syndrome)
• self mutilation, MR, Uric aciduria
• mother is the carrier
• 1/2 of sons have the disease
• 1/2 of daughter are carriers
• carrier state can be detected
• prenatal diagnosis is possible

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Single major locus (cont)

• Disorders of gene and chromosome numbers
• Trisomy 21 (Downs)
• XYY more common in jails than society
• not related to an elevation of testosterone and
  aggression
• probably due to a lower intellectual function of
  XYY patients

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Personality

• Cloningers 3 dimensional model
• novelty seeking
• harm avoidance
• reward dependence
• Some traits have a high inheritance
• antisocial is greater than rheumatoid arthritis
• Clear role for socialization and environment

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Intelligence

• MZ twins scores on IQ tests have a correlation of
  80-90
• whether reared together or separately
• DZ twins have correlation of about 50
• heritability factor of about 50-70
• Inverse relationship of MR offspring and parents

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Schizophrenia

• lifetime population risk of 1
• risk to sibs and children of index case is 8-12
• risk to parents is 5
• may reflect fact that sicker patients dont marry

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Schizophrenia (cont)

• MZ concordance of 40-70
• DZ concordance of 8-20
• second trimester hypothesis
• time of neural specialization
• frontal injury hypothesis

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Bipolar disorder

• Lifetime risk about 1
• sexes are equally affected
• risk to 1st degree relative is 8-20
• MZ risk-65-70
• DZ risk-15
• linkage studies suggest chromosome 11 and x-linked

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Unipolar

• lifetime risk is 6-10
• 2-3 times more common is women
• risk to first degree relatives is 10-20
• MZ risk-40
• DZ risk-11
• phenotypic expression-undiagnosed bipolar
  disorder for ex.

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Alcoholism

• lifetime risk-
• 3-5 for men
• 0.5 - 1 for women
• 25 of male first degree relatives
• 3-10 of female first degree relatives

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Alcoholism

• twin risk depends on definitions
• MZ risk-
• 60 (Swedish studies)
• 25 (US)
• DZ risk
• 30 (Swedish)
• 12 (US)
• runs with affective disorders in families

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Alcoholism

• RFLP
• dopamine 2 receptor alleles
• Dopamine receptor D2 receptor allele known as
  Taql B1 is reported as a marker for severe
  familial alcoholism
• Aldehyde dehydrogenase
• enzyme which metabolizes alcohol is found in
  varying degrees of activity in various cultures

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Alzheimers Disease

• Difficult to study due to death before expression
  of gene for SDAT
• 19 risk for 1st degree relatives
• increases with survival age
• 50 if you live to 80 y/o

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SDAT

• two forms
• early onset (prior to 65)
• linked to chromosome 21
• Late onset (after 60)
• linked to chromosome 19