Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies

Gary A. Heiman, Elizabeth Leigh Ogburn, Prakash Gorroochurn, Katherine M. Keyes, Deborah Hasin

Research output: Contribution to journalArticle

Abstract

Some twin studies suggest that substance initiation and dependence are part of a complex, two-stage process and that some genetic influences are stage-specific, acting on either the transition from abstinence to initiation, or on the transition from use to dependence. However, questions remain about the two-stage model, especially for illicit drugs. Using a familial aggregation design, we tested the hypothesized two-stage model of dependence on illicit substances and alcohol in a large, nationally representative sample. Family history of drug or alcohol problems is significantly associated with initiation that does not progress to dependence (i.e., conditional initiation). Furthermore, family history of drug or alcohol problems is significantly associated with dependence even after conditioning on factors influencing initiation (i.e., conditional dependence). These results suggest that substance initiation and dependence involve at least partially distinct familial factors. The possibility that different genetic factors affect initiation and dependence has important implications for control group selection in case-control genetic association studies, and may explain some inconsistent results for drug dependence. If some genetic factors are stage-specific (i.e., not common across initiation and dependence), inclusion of abstainers in the control group may mix the genetic effects for initiation with those for transition to dependence, providing unclear results. Depending on the specific question about the nature of the genetic effect (whether on initiation, on dependence, or both), investigators designing case-control genetic association studies should carefully consider inclusion and exclusion criteria of the control group.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalDrug and Alcohol Dependence
Volume92
Issue number1-3
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Genetic Association Studies
Substance-Related Disorders
Peptide Initiation Factors
Alcohols
Control Groups
Genetic Phenomena
evidence
Twin Studies
Street Drugs
Pharmaceutical Preparations
Research Personnel
heredity
alcohol
drug
genealogy
Agglomeration
inclusion
twin studies
Group
drug dependence

Keywords

  • Alcohol dependence
  • Conditional dependence
  • Control group selection
  • Drug dependence
  • Familial aggregation
  • Genetic association

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies. / Heiman, Gary A.; Ogburn, Elizabeth Leigh; Gorroochurn, Prakash; Keyes, Katherine M.; Hasin, Deborah.

In: Drug and Alcohol Dependence, Vol. 92, No. 1-3, 01.01.2008, p. 258-266.

Research output: Contribution to journalArticle

Heiman, Gary A. ; Ogburn, Elizabeth Leigh ; Gorroochurn, Prakash ; Keyes, Katherine M. ; Hasin, Deborah. / Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies. In: Drug and Alcohol Dependence. 2008 ; Vol. 92, No. 1-3. pp. 258-266.
@article{bb2fd323e9ac455280c12c27ececc09a,
title = "Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies",
abstract = "Some twin studies suggest that substance initiation and dependence are part of a complex, two-stage process and that some genetic influences are stage-specific, acting on either the transition from abstinence to initiation, or on the transition from use to dependence. However, questions remain about the two-stage model, especially for illicit drugs. Using a familial aggregation design, we tested the hypothesized two-stage model of dependence on illicit substances and alcohol in a large, nationally representative sample. Family history of drug or alcohol problems is significantly associated with initiation that does not progress to dependence (i.e., conditional initiation). Furthermore, family history of drug or alcohol problems is significantly associated with dependence even after conditioning on factors influencing initiation (i.e., conditional dependence). These results suggest that substance initiation and dependence involve at least partially distinct familial factors. The possibility that different genetic factors affect initiation and dependence has important implications for control group selection in case-control genetic association studies, and may explain some inconsistent results for drug dependence. If some genetic factors are stage-specific (i.e., not common across initiation and dependence), inclusion of abstainers in the control group may mix the genetic effects for initiation with those for transition to dependence, providing unclear results. Depending on the specific question about the nature of the genetic effect (whether on initiation, on dependence, or both), investigators designing case-control genetic association studies should carefully consider inclusion and exclusion criteria of the control group.",
keywords = "Alcohol dependence, Conditional dependence, Control group selection, Drug dependence, Familial aggregation, Genetic association",
author = "Heiman, {Gary A.} and Ogburn, {Elizabeth Leigh} and Prakash Gorroochurn and Keyes, {Katherine M.} and Deborah Hasin",
year = "2008",
month = "1",
day = "1",
doi = "10.1016/j.drugalcdep.2007.08.007",
language = "English (US)",
volume = "92",
pages = "258--266",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
publisher = "Elsevier Ireland Ltd",
number = "1-3",

}

TY - JOUR

T1 - Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies

AU - Heiman, Gary A.

AU - Ogburn, Elizabeth Leigh

AU - Gorroochurn, Prakash

AU - Keyes, Katherine M.

AU - Hasin, Deborah

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Some twin studies suggest that substance initiation and dependence are part of a complex, two-stage process and that some genetic influences are stage-specific, acting on either the transition from abstinence to initiation, or on the transition from use to dependence. However, questions remain about the two-stage model, especially for illicit drugs. Using a familial aggregation design, we tested the hypothesized two-stage model of dependence on illicit substances and alcohol in a large, nationally representative sample. Family history of drug or alcohol problems is significantly associated with initiation that does not progress to dependence (i.e., conditional initiation). Furthermore, family history of drug or alcohol problems is significantly associated with dependence even after conditioning on factors influencing initiation (i.e., conditional dependence). These results suggest that substance initiation and dependence involve at least partially distinct familial factors. The possibility that different genetic factors affect initiation and dependence has important implications for control group selection in case-control genetic association studies, and may explain some inconsistent results for drug dependence. If some genetic factors are stage-specific (i.e., not common across initiation and dependence), inclusion of abstainers in the control group may mix the genetic effects for initiation with those for transition to dependence, providing unclear results. Depending on the specific question about the nature of the genetic effect (whether on initiation, on dependence, or both), investigators designing case-control genetic association studies should carefully consider inclusion and exclusion criteria of the control group.

AB - Some twin studies suggest that substance initiation and dependence are part of a complex, two-stage process and that some genetic influences are stage-specific, acting on either the transition from abstinence to initiation, or on the transition from use to dependence. However, questions remain about the two-stage model, especially for illicit drugs. Using a familial aggregation design, we tested the hypothesized two-stage model of dependence on illicit substances and alcohol in a large, nationally representative sample. Family history of drug or alcohol problems is significantly associated with initiation that does not progress to dependence (i.e., conditional initiation). Furthermore, family history of drug or alcohol problems is significantly associated with dependence even after conditioning on factors influencing initiation (i.e., conditional dependence). These results suggest that substance initiation and dependence involve at least partially distinct familial factors. The possibility that different genetic factors affect initiation and dependence has important implications for control group selection in case-control genetic association studies, and may explain some inconsistent results for drug dependence. If some genetic factors are stage-specific (i.e., not common across initiation and dependence), inclusion of abstainers in the control group may mix the genetic effects for initiation with those for transition to dependence, providing unclear results. Depending on the specific question about the nature of the genetic effect (whether on initiation, on dependence, or both), investigators designing case-control genetic association studies should carefully consider inclusion and exclusion criteria of the control group.

KW - Alcohol dependence

KW - Conditional dependence

KW - Control group selection

KW - Drug dependence

KW - Familial aggregation

KW - Genetic association

UR - http://www.scopus.com/inward/record.url?scp=36849028696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36849028696&partnerID=8YFLogxK

U2 - 10.1016/j.drugalcdep.2007.08.007

DO - 10.1016/j.drugalcdep.2007.08.007

M3 - Article

C2 - 17933473

AN - SCOPUS:36849028696

VL - 92

SP - 258

EP - 266

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

SN - 0376-8716

IS - 1-3

ER -