Genome wide association for substance dependence

Convergent results from epidemiologic and research volunteer samples

Catherine Johnson, Tomas Drgon, Qing Rong Liu, Pingwu Zhang, Donna Walther, Chuan Yun Li, James C. Anthony, Yulan Ding, William W Eaton, George R. Uhl

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number113
JournalBMC Medical Genetics
Volume9
DOIs
StatePublished - Dec 18 2008

Fingerprint

Baltimore
Substance-Related Disorders
Volunteers
Genome
Single Nucleotide Polymorphism
Sampling Studies
Research
Molecular Biology
Expressed Sequence Tags
Amygdala
Gene Frequency
Genes
Hippocampus
Brain

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Genome wide association for substance dependence : Convergent results from epidemiologic and research volunteer samples. / Johnson, Catherine; Drgon, Tomas; Liu, Qing Rong; Zhang, Pingwu; Walther, Donna; Li, Chuan Yun; Anthony, James C.; Ding, Yulan; Eaton, William W; Uhl, George R.

In: BMC Medical Genetics, Vol. 9, 113, 18.12.2008.

Research output: Contribution to journalArticle

Johnson, Catherine ; Drgon, Tomas ; Liu, Qing Rong ; Zhang, Pingwu ; Walther, Donna ; Li, Chuan Yun ; Anthony, James C. ; Ding, Yulan ; Eaton, William W ; Uhl, George R. / Genome wide association for substance dependence : Convergent results from epidemiologic and research volunteer samples. In: BMC Medical Genetics. 2008 ; Vol. 9.
@article{86283184e7784eb1a2548d2bbab3c68d,
title = "Genome wide association for substance dependence: Convergent results from epidemiologic and research volunteer samples",
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.",
author = "Catherine Johnson and Tomas Drgon and Liu, {Qing Rong} and Pingwu Zhang and Donna Walther and Li, {Chuan Yun} and Anthony, {James C.} and Yulan Ding and Eaton, {William W} and Uhl, {George R.}",
year = "2008",
month = "12",
day = "18",
doi = "10.1186/1471-2350-9-113",
language = "English (US)",
volume = "9",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Genome wide association for substance dependence

T2 - Convergent results from epidemiologic and research volunteer samples

AU - Johnson, Catherine

AU - Drgon, Tomas

AU - Liu, Qing Rong

AU - Zhang, Pingwu

AU - Walther, Donna

AU - Li, Chuan Yun

AU - Anthony, James C.

AU - Ding, Yulan

AU - Eaton, William W

AU - Uhl, George R.

PY - 2008/12/18

Y1 - 2008/12/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=59849090159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=59849090159&partnerID=8YFLogxK

U2 - 10.1186/1471-2350-9-113

DO - 10.1186/1471-2350-9-113

M3 - Article

VL - 9

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

M1 - 113

ER -