TABLE  1.  Classical and molecular genetic approaches for studying human vulnerability to substance abuse



Problems and limitationsa

Classical Genetic Studies



Family studies

•  Determine if family members of substance

abusers are at increased risk for substance

•  Generational and secular trends in drug




•  Nonpaternity.


•  Provide evidence consistent with a genetic basis

for the disorder (not conclusive).

•  Inability to separate genetic from family

environmental effects.

Segregation analyses

•  Use the diagnostic status of family members to

•  Affected by statistical non-normality.


determine the relative likelihood of alternative

modes of transmission for a familial disorder

(e.g., polygenic, single major locus, mixed).

•  No direct test of single locus versus

polygenic model of transmission.

Twin studies

•  Determine if within-pair similarity for substance

abuse is greater in genetically identical twins

than in 50% genetically identical fraternal twins.

•  Requires accurate zygosity


•  Assumes equal relevant environments in



identical and fraternal twins.

•  Rare subjects.

Adoption studies

•  Separate the effects of genes and environment

•  Assumes no selective placement.


by studying the similarity between biological

parents, their adopted-away children, and their

adoptive parents.

•  Places prenatal environmental effects in

the “genetic” component.

•  Rarity of subjects.

Molecular genetic studies



Linkage analyses

•  To use family data to statistically link a trait to a

•  Multiple statistical comparisons.


genetic marker on a particular chromosome.

•  Assumes particular mode of




•  Rare multigenerational drug abuse




•  Generational and secular trends.

Association studies

•  To compare genetic variation at a specific site in

affected and unaffected individuals.

•  Appropriate control group.

  a Problems common to all methods include: diagnostic imprecision, variable age of onset, etiological heterogeneity, assortative mating, and ascertainment bias.
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published 2000