Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Dec 18:9:113.
doi: 10.1186/1471-2350-9-113.

Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples

Catherine Johnson  1 , Tomas Drgon, Qing-Rong Liu, Ping-Wu Zhang, Donna Walther, Chuan-Yun Li, James C Anthony, Yulan Ding, William W Eaton, George R Uhl
Affiliations

Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples

Catherine Johnson et al. BMC Med Genet. .

Abstract

Background: Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers.

Results: We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent vs control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance.

Conclusion: The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Substantial overlaps of the zip codes in which subjects reported their residences. Fractional distributions (X axis) of zip codes (Y axis) in which ECA (solid blue bars) or MNB (dotted purple bars) subjects reported their residence. Areas from which NIDA and ECA recruitment efforts were dissimilar include 21214; Lauraville and surrounding areas and 21222, Dundalk and surrounding areas. Zip codes from which fewer than 3 individuals were recruited are not indicated.
See this image and copyright information in PMC

References

    1. Uhl GR, Elmer GI, Labuda MC, Pickens RW. Genetic influences in drug abuse. In: Gloom FE, Kupfer DJ, editor. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press; 1995. pp. 1793–2783.
    1. Tsuang MT, Lyons MJ, Meyer JM, Doyle T, Eisen SA, Goldberg J, True W, Lin N, Toomey R, Eaves L. Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry. 1998;55:967–972. doi: 10.1001/archpsyc.55.11.967. - DOI - PubMed
    1. Karkowski LM, Prescott CA, Kendler KS. Multivariate assessment of factors influencing illicit substance use in twins from female-female pairs. Am J Med Genet. 2000;96:665–670. doi: 10.1002/1096-8628(20001009)96:5<665::AID-AJMG13>3.0.CO;2-O. - DOI - PubMed
    1. True WR, Heath AC, Scherrer JF, Xian H, Lin N, Eisen SA, Lyons MJ, Goldberg J, Tsuang MT. Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms. Am J Med Genet. 1999;88:391–397. doi: 10.1002/(SICI)1096-8628(19990820)88:4<391::AID-AJMG17>3.0.CO;2-L. - DOI - PubMed
    1. Kendler KS, Karkowski LM, Neale MC, Prescott CA. Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Arch Gen Psychiatry. 2000;57:261–269. doi: 10.1001/archpsyc.57.3.261. - DOI - PubMed

Publication types