Genome-wide search for replicable risk gene regions in alcohol and nicotine co-dependence.

paper Cited Public

Authors: Zuo, Lingjun; Zhang, Fengyu; Zhang, Heping; Zhang, Xiang-Yang; Wang, Fei; Li, Chiang-Shan R; Lu, Lingeng; Hong, Jiang; Lu, Lin; Krystal, John; Deng, Hong-Wen; Luo, Xingguang
Year: 2012
Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
PMID: 22488850
DOI: 10.1002/ajmg.b.32047
PMCID: PMC3405545

#	Section	Preview
0	Introduction	Alcohol dependence (AD) and nicotine dependence (ND) frequently co-occur in the same individuals.…
1	Introduction	In the present study, we searched for replicable risk gene regions for alcohol and nicotine…
2	Materials and Methods — Subjects	The sample comprised of a total of 3,143 subjects for gene-disease association analysis, including…
3	Materials and Methods — Subjects	had never become dependent on or abused alcohol, nicotine or other illicit substances (see…
4	Materials and Methods — Genotyping	All samples were genotyped on the Illumina Human 1M beadchip at the Center for Inherited Disease…
5	Materials and Methods — Data cleaning	Before statistical analysis, we strictly cleaned the phenotype data and then the genotype data [Zuo…
6	Materials and Methods — Data analytic procedure	We performed genome-wide association analysis separately in EAs and AAs first, and then performed a…
7	Materials and Methods — Data analytic procedure	In addition to the replication design described above, we also performed functional eQTL analysis on…
8	Materials and Methods — Correction for multiple testing on association and cis-eQTL analysis and power analysis	To mitigate false positive rates, genome-wide associations in the screening stage need to be…
9	Materials and Methods — Correction for multiple testing on association and cis-eQTL analysis and power analysis	the testing step, (1) two independent samples were used to replicate each other, which significantly…
10	Results	There were a total of 29 SNPs in 15 genes in EAs, 9 SNPs in 9 genes in AAs and 22 SNPs in 16 genes…
11	Results	significant SNPs, only rs9636470 in PLGLB2 (p=2.4×10-6 in EAs and 0.004 in AAs) and rs1318937 in…
12	Results	Throughout the whole chromosome 3, SH3BP5-NR2C2 region was the only one that had gene-disease…
13	Results	SH3BP5-NR2C2 region contains five known genes including SH3BP5, CAPN7, ZFYVE20, MRPS25 and NR2C2,…
14	Results	The LD structure (Figure 1d), the gene effect directions and the gene effect sizes shown in Table 1…
15	Results	Our samples had a high power in detecting risk markers. For example, given that the risk allele of…
16	Results	Among those 11 replicable risk markers, four SNPs were available for eQTL analysis, including…
17	Results	Genome-wide trans-eQTL analysis showed that transcript expression of genes in SH3BP5-NR2C2 region…
18	Results	Transcriptome-wide expression correlation analysis showed that expression of NR2C2, ZFYVE20, CAPN7…
19	Results	The main findings from the RNA secondary structure analysis included that (1) rs9868848 in ZFYVE20…

Name	Type
AA	cohort
acetylcholine	drug
ADH5	gene
African American	cohort
African-American cases local	cohort
African-Americans	cohort
alcohol	phenotype
alcohol and nicotine co-dependence local	phenotype
Alcohol and nicotine co-dependence local	phenotype
alcohol dependence	phenotype
Alcohol-nicotine co-dependence local	phenotype
ALDH3A2 local	gene
anxiety	phenotype
brain	anatomy
brain tissue	anatomy
CAPN7 local	gene
CCBE1 local	gene
Center for Inherited Disease Research	cohort
cholinergic	drug
Chrm1	gene
CHRNA1	gene
Chrna3	gene
CHRNA5-CHRNA3-CHRNB4 cluster	gene
CHRNA6-CHRNB3 local	gene
Chrna7	gene
Chrnb2	gene
CHRND	gene
CHRNG	gene
Cnr1	gene
cocaine	phenotype
controls	cohort
cortical brain tissues local	anatomy
CTNNA3	gene
CTTNBP2 local	gene
dopamine	drug
Dopaminergic system	drug
DRD1	gene
DRD2	gene
DRD3	gene
DRD4	gene
EA	cohort
EAs	cohort
EA sample	cohort
endocannabinoids	drug
endocannabinoid system	drug
European-American cases local	cohort
European ancestry	cohort
European population	cohort
exon-level cis-eQTL findings local	phenotype
FAM47B	gene
GABA	phenotype
GABARAP	gene
Gabbr1	gene
Gabra1	gene
GABRA2	gene
Gabra4	gene
GABRA6	gene
GABRB1	gene
Gabrb2	gene
Gabrb3	gene
Gabrg1	gene
Gabrg2	gene
Gabrg3	gene
GAD1	gene
glutamate	drug
glutamatergic system	drug
GRIK2	gene
GRIK3	gene
GRIN2A	gene
GRIN2B	gene
GRIN2C	gene
GRM5	gene
GRM7	gene
HAO2 local	gene
histamine	drug
HNMT local	gene
Htr1a	gene
Htr1b	gene
Htr2a	gene
Htr3b	gene
illicit drugs	phenotype
Illumina BeadStudio Genotyping Module local	drug
Illumina Human1M array	drug
independent samples	cohort
IPO11 local	gene
ITGA4 local	gene
KCNN3	gene
KIAA0040	gene
Major axis I disorders local	phenotype
meta-analysis	cohort
mood disorders	phenotype
MRPS25 local	gene
NCAM1	gene
neuropeptide local	drug
nicotine	drug
nicotine dependence	phenotype
NIDA/MNB	cohort
NPY1R	gene
NPY2R	gene
NPY5R	gene
NR2C2 local	gene
opioid	drug
Opioid system	drug
Oprd1	cohort
OPRM1	cohort
PARK2	gene
PBK local	gene
PBMC local	anatomy
PBMC local	cohort
peripheral blood mononucleated cells local	drug
Peripheral blood mononucleated cells local	cohort
PET112L local	gene
phenotype	phenotype
PKNOX2	gene
PLEKHG1 local	gene
PLGLB2 local	gene
polysubstance local	drug
polysubstance dependence	phenotype
Pomc	gene
replicable risk genes local	gene
replicable risk SNPs local	variant
rs1318937 local	variant
rs17040623 local	variant
rs17427389 local	variant
rs2169520 local	variant
rs2306853 local	variant
rs28445844 local	variant
rs4610908 local	variant
rs4700575 local	variant
rs735659 local	variant
rs7445832 local	variant
rs7667919 local	variant
rs8225 local	variant
rs9310472 local	variant
rs9636470 local	variant
rs9868848 local	variant
SAGE	cohort
SAGE dataset	cohort
schizophrenia	phenotype
Serotonergic system	drug
serotonin	drug
SGCZ local	gene
SH3BP5 local	gene
SH3BP5-NR2C2 region local	gene
SLC6A3	gene
SLC6A4	gene
SNP	cohort
Th	gene
TMEM47 local	gene
TTC12	gene
Wellcome Trust case control consortium	cohort
ZFYVE20 local	gene

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In this knowledge base

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Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking.	2015	25542586
Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression.	2014	25129674

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