# Presentation: 725682

## Genetic Epidemiological Perspectives on Alcohol Use and Dependence

- Society for Neuroscience:
- Henri Begleiter Symposium
- 11/2/07
- Kenneth S Kendler MD
- Virginia Institute for Psychiatric and Behavioral Genetics

## Outline of Talk

- Examine the specificity of genetic risk factors for alcohol abuse/dependence.
- Explore the changing role of shared environment and genes in influencing alcohol intake over development.
- Examine the sources of individual differences over development in self-ratings of alcohol availability.

## Outline of Talk

- 	4. Determine the role of genetic factors in determining the social environment.
- 	5. Use genetic epidemiological methods to disentangle the causal inter-relationships between person and peer group deviance.

## Specifity of Genetic Risk Factors for Alcohol Abuse/Dependence

- Sample -- over 4,500 members of male and female twin pairs from the Virginia Twin Registry, all personally interviewed.
- First analysis --  7 common psychiatric and substance use disorders assessed at personal interview.
- Second analysis – Abuse/dependence of 5 psychoactive substances
- 3  licit:  caffeine, nicotine and alcohol
- 2 illicit substances:  cannabis and cocaine.

## Illicit Substance

- Genetic Factor

**Alcohol**
**Dependence**

- Cannabis
- Dependence

- Cocaine
- Dependence

- Nicotine
- Dependence

- A

- A

- A

- A

- E

- E

- E

- E

- E1

- .68

- .82

- .35

- .20

- .31

- .68

- .37

- .27

- .48

- .18

- .53

- .47

- .28

- .48

- Caffeine
- Dependence

- A

- .56

- E

- .14

- .80

- Licit Substance
- Genetic Factor

- .77

- .52

- .15

- .82

- Alcohol
- Dependence

- Cannabis
- Dependence

- Cocaine
- Dependence

- Nicotine
- Dependence

- Caffeine
- Dependence

## Genetic Sources of Comorbidity in Common Psychiatric And Drug Use  Disorders

**Genetic Sources of Comorbidity in Common Psychiatric And Drug Use  Disorders**

- DEP = dependence
- GAD = generalized anxiety disorder

## Individual Differences in Psychoactive Substance Use Across the LifeSpan

- Use of calendar data from this same sample.
- Useful data on nicotine, caffeine, alcohol and cannabis. Will only look at alcohol use here.
- Look at univariate results across years of age

## Sources of Individual Differences in Self-Report Alcohol Availability

- Measures of average alcohol intake  retrospectively reported by the  life history method for each year up to their present age.
- ~750 male-male twin pairs.
- From the third interview wave with male-male twins, completed in 1998-2004 by 1796 male twins (75%) who had participated in the second interview. Subjects were 24-62 years old (mean age = 40.3 years, SD = 9.0).

## ALCOHOL

## Slide 10

## Slide 12

## Models of Development

- How to begin to understand the developmental  pathways through which genetic and environmental risk factors contribute to externalizing disorders.
- Do we need to move away from the static model of genetic effects that are often assumed in cross-sectional twin studies and in linkage and association studies?

## Examples of Items for PGD

- How many of your friends would have
- Smoked cigarettes
- Had problems with alcohol
- Been in trouble with the law
- Cheated on school tests
- Sold or gave drugs to other kids

## Modeling Time and the Environment Together – Dynamic Changes in our Social Environment 

- Measures of peer group deviance retrospectively reported by the  life history method.
- ~750 male-male twin pairs.
- Five ages assessed.
- The third interview wave, restricted to male-male twins, was completed in 1998-2004 by 1796 male twins (75%) who had participated in the second interview. Subjects were 24-62 years old (mean age = 40.3 years, SD = 9.0).

## Slide 16

## Slide 17

## Slide 18

## Slide 19

## Joint Developmental Models for PGD and CD

- Same Sample
- Focus on 3 waves – the relationship between personal deviance (CD) and Peer group deviance (PGD)
- Major prior theories
- Role of **social selection** CD to PD
- Versus **social causation**  PD to CD

## Slide 21

## Models of Development

- Conclusions
- Variance in peer group deviance grows dramatically with age – most of this is driven by increasing genetic effects. Genes influence how we shape our social world.

## Models of Development

- Conclusions
- Analyses of CD and PD were very illuminating about causal processes. Seems that genetic epidemiologic methods are here able to cleanly divide causal processes – social selection and social causation --  in ways that would be hard to see doing with other methods.

## Summary of Talk

- Genetic risk factors for alcohol abuse/dependence are partly specific and partly non-specific.
- In early adolescence, shared environmental factors play an important role in individual differences in alcohol intake. With increasing age, genetic factors become more important.

## Summary of Talk

- 	3. Examine the sources of individual differences over development in self-ratings of alcohol availability.
- 	4. Through development, genetic factors become increasingly important in influencing our choice of social environment.
- 	5. Genes appear to drive processes of social selection (from individual to peer deviance) while shared environmental factors drive social causation (from peer to individual deviance).

## Summary of Talk

- 	6. Implications of these findings for molecular genetic studies of alcohol dependence.

## Thanks

- Lindon Eaves
- John Myers
- Eric Schmitt
- Charles Gardner
- Steve Aggen
- Carol Prescott
- Nathan Gillispie
- NIH grants AA-011408 and DA-011287
- And always, the twins.