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


CONCLUSIONS
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.
Johnson
Catherine
C
Molecular Neurobiology Branch, NIH-IRP (NIDA), Suite 3510, 333 Cassell Drive Baltimore, Maryland 21224, USA. johnsoncat@intra.nida.nih.gov
Drgon
Tomas
T
Liu
Qing-Rong
QR
Zhang
Ping-Wu
PW
Walther
Donna
D
Li
Chuan-Yun
CY
Anthony
James C
JC
Ding
Yulan
Y
Eaton
William W
WW
Uhl
George R
GR
D000483:Alleles; D015142:Baltimore / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*; D044465:White People