KAT2B polymorphism identified for drug abuse in African Americans with regulatory links to drug abuse pathways in human prefrontal cortex.

paper Primary Public

Authors: Johnson, Eric O; Hancock, Dana B; Levy, Joshua L; Gaddis, Nathan C; Page, Grier P; Glasheen, Cristie; Saccone, Nancy L; Bierut, Laura J; Kral, Alex H
Year: 2016
Journal: Addiction biology
PMID: 26202629
DOI: 10.1111/adb.12286
PMCID: PMC4724343

#	Section	Preview
0	INTRODUCTION	Drug abuse is a major public health burden with profound personal and societal consequences. Abuse…
1	INTRODUCTION	Genetic associations have been established for CHRNA5/A3/B4 polymorphisms with cigarette…
2	INTRODUCTION	subjects, identified only nominally significant SNP associations.(Agrawal et al., 2014; Liu et al.,…
3	MATERIALS and METHODS — Drug Abuse Cases from the Urban Health Study (UHS)	Drug abuse cases were drawn from the UHS, one of the largest studies of street-recruited PWID in…
4	MATERIALS and METHODS — Drug Abuse Cases from the Urban Health Study (UHS)	met the Office of National Drug Control Policy definition of heroin abuse by using 10 or more times…
5	MATERIALS and METHODS — Drug Abuse Cases from the Urban Health Study (UHS)	To assess the correspondence between definition of a drug abuse case used here (past 30 day…
6	MATERIALS and METHODS — Population Controls	Drug abuse cases from the UHS were compared to population controls assembled using the pipeline…
7	MATERIALS and METHODS — Population Controls	Two of the selected control cohorts were ascertained for addiction phenotypes: Collaborative Genetic…
8	MATERIALS and METHODS — Population Controls	Using unassessed population controls carries the possibility of misclassifying true cases as a…
9	MATERIALS and METHODS — Quality Control and Genotype Imputation	Prior evaluations have shown that GWAS can be validly conducted with cases compared to population…
10	MATERIALS and METHODS — Quality Control and Genotype Imputation	Before combining the UHS drug abuse cases in each ancestry group with population controls of the…
11	MATERIALS and METHODS — Quality Control and Genotype Imputation	Our final analysis data set included 3,742 AAs (2,017 UHS cases and 1,725 population controls) and…
12	MATERIALS and METHODS — Quality Control and Genotype Imputation	Genome-wide genotype imputation of SNPs and insertion/deletion polymorphisms (indels) was conducted…
13	MATERIALS and METHODS — Discovery GWAS Analyses	GWAS analyses were conducted in each ancestry group to test the imputed SNP and indel genotype…
14	MATERIALS and METHODS — Discovery GWAS Analyses	The GWAS resulted in λgc=1.036 for AAs (Figure S1a) and λgc=1.069 for EAs (Figure S1b). Given the…
15	MATERIALS and METHODS — Replication Study Cohort and Analyses	One dbGaP cohort with drug abuse data available on both AA and EA participants was utilized for…
16	MATERIALS and METHODS — Replication Study Cohort and Analyses	As described in Shi et al.,(Shi et al., 2009) GAIN controls were recruited from the general…
17	MATERIALS and METHODS — Replication Study Cohort and Analyses	(273 cases and 858 controls), who passed quality control, had complete DSM-IV and covariate data…
18	MATERIALS and METHODS — Replication Study Cohort and Analyses	The GAIN EAs and AAs were analyzed separately. Genotyped SNPs passing quality control were used as…
19	MATERIALS and METHODS — Bioinformatics Analyses	Linkage disequilibrium patterns were discerned using LocusZoom (Pruim et al., 2010) with populations…

Name	Type
1000 Genomes AFR local	cohort
1000 Genomes Project	cohort
AA	cohort
AA cohorts	cohort
AA-specific GWAS local	cohort
addiction	phenotype
addiction phenotypes	phenotype
ADH1B	gene
AFR	cohort
African	cohort
African American	cohort
alcohol	phenotype
alcohol abuse	phenotype
alcohol dependence	phenotype
ALDH2	gene
Amphetamines/stimulants local	drug
Amphetamine/stimulant abuse local	phenotype
amphetamine/stimulants local	drug
Amphetamine/stimulants local	drug
behavioral response to cocaine local	phenotype
Biased genotype-phenotype associations local	phenotype
BiGS local	cohort
bipolar disorder	phenotype
BrainCloud	cohort
BrainCloud local	drug
BrainCloud cohort local	cohort
BrainCloud project local	cohort
C17orf58	gene
cases cohort local	cohort
Chrna3	gene
CHRNA5	gene
Chrnb4	gene
cigarettes	phenotype
cocaine	phenotype
COGEND	cohort
control data sets local	cohort
control population	cohort
controls cohort local	cohort
CREB1	gene
CREBBP	gene
Cross-Disorder Group of the Psychiatric Genomics local	cohort
CRTC2 local	gene
dbGaP	cohort
Dependence symptoms	phenotype
discovery sample	cohort
dorsolateral prefrontal cortex	anatomy
Drug Abuse Case (30-day injection + ≥10 uses) local	phenotype
Drug Abuse Cases Cohort local	cohort
Drug Abuse GWAS Cohort local	cohort
Drug abuse phenotype local	phenotype
Drug Abuse Phenotype local	phenotype
drug abuse phenotypes local	phenotype
drug dependence	phenotype
drug rewarding effects local	phenotype
drugs	drug
drug-seeking behavior	phenotype
DSM criteria	phenotype
DSM-IV	phenotype
DSM-IV Drug Abuse/Dependence local	phenotype
DSM-IV marijuana local	phenotype
EA	cohort
EAs	cohort
EA-specific GWAS local	cohort
EUR	cohort
European ancestry	cohort
expression level local	phenotype
FLJ30838 local	gene
frontal cortex	anatomy
GAIN	cohort
GAIN AAs local	cohort
GAIN African Americans local	cohort
GAIN cohort local	cohort
GAIN European Americans local	cohort
Genetic Association Information Network (GAIN) GWAS of Schizophrenia local	cohort
genetic variants	cohort
GWAS meta-analysis (both ancestry groups) local	cohort
HapMap3	cohort
heavy drinking	phenotype
heroin/opioids local	drug
Heroin/opioids local	drug
human brain	anatomy
illicit drugs	phenotype
illicit drug use	phenotype
Impute2	drug
imputed SNP and indel genotype dosages local	variant
imputed SNPs	variant
indel	variant
injection local	drug
Injection Drug Use Phenotype local	phenotype
KAT2B	gene
KYNU local	gene
lower CREBBP expression local	phenotype
MAML1 local	gene
marijuana	phenotype
marijuana abuse	phenotype
marijuana dependence	phenotype
marijuana use disorder	phenotype
mood disorders	phenotype
multiancestry GWAS meta-analysis local	cohort
multi-drug abuse	phenotype
National Surveys on Drug Use and Health local	cohort
natural opioids local	drug
nicotine	drug
nicotine dependence	phenotype
NSDUH	cohort
nucleus accumbens	anatomy
opioid	drug
opioid dependence	phenotype
OPRM1	cohort
other drug dependence	phenotype
other drugs	drug
People who inject drugs (PWID) local	cohort
Population Controls Cohort local	cohort
post-mortem dorsolateral prefrontal cortex samples local	anatomy
prefrontal cortex	anatomy
psychiatric disorders	phenotype
putamen	anatomy
PWID local	cohort
PWID local	phenotype
PWIDs local	cohort
Replication Study Cohort local	cohort
reward sensitivity	phenotype
rs17552189 local	variant
rs2381356 local	variant
rs8071463 local	variant
rs9829896	variant
rs9891146 local	variant
rs9891146-T local	variant
rs9897982 local	variant
SAGE	cohort
schizophrenia	phenotype
Schizophrenia Working Group of the Psychiatric Genomics local	cohort
smoking	phenotype
SNP	cohort
stimulants	drug
study cohort	cohort
synthetic opioids local	drug
temperament	phenotype
True cases local	phenotype
UHS	cohort
UHS drug abuse cases local	cohort
UHS subjects local	cohort
United States	cohort

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Human Genetics of Addiction: New Insights and Future Directions.	2018	29504045

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