Replication of ZNF804A gene variant associations with risk of heroin addiction.

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Authors: Hancock, D B; Levy, J L; Gaddis, N C; Glasheen, C; Saccone, N L; Page, G P; Bierut, L J; Kral, A H; Johnson, E O
Year: 2015
Journal: Genes, brain, and behavior
PMID: 26382569
DOI: 10.1111/gbb.12254
PMCID: PMC4715582

#	Section	Preview
0	Introduction	Addiction to heroin and other opioid drugs is a growing public health concern (Substance Abuse and…
1	Introduction	Novel associations between SNPs in the zinc finger protein 804A (ZNF804A) gene and heroin addiction…
2	Introduction	to drive both schizophrenia (Nieratschker et al., 2010) and addiction (Hyman et al., 2006). In…
3	Materials and Methods — Study participants	Heroin addiction cases were drawn from the Urban Health Study (UHS) of street-recruited people who…
4	Materials and Methods — Study participants	The UHS heroin addiction cases were compared to population controls assembled together from six…
5	Materials and Methods — Study participants	All study protocols received Institutional Review Board approval at their respective sites, and all…
6	Materials and Methods — Genotyping and Quality Control	As detailed elsewhere (Hancock et al., in press, Johnson et al., 2015), stored serum samples from…
7	Materials and Methods — Genotyping and Quality Control	The genotyped participants’ ancestral proportions were determined using the STRUCTURE program…
8	Materials and Methods — Statistical analyses	Additive SNP genotypes were tested for association with heroin addiction, separately by ancestry,…
9	Materials and Methods — Statistical analyses	To infer the haplotypes occurring between the two ZNF804A SNPs, we phased the study genotypes in…
10	Results	The ZNF804A SNP association results are shown in Table 2. Rs7597593-T was the minor allele in…
11	Results	Of the 10,757 participants in our dataset, 45.8% were female (Table 1). We tested both SNPs for…
12	Results	High D′ values between rs7597593 and rs1344706 indicated strong linkage disequilibrium (D′=1 in…
13	Results	The two-SNP haplotype associations with heroin addiction are presented in Table 3. Haplotypes…
14	Results	Table 1 shows that a large portion of our heroin addiction cases also reported abuse (using 10 or…
15	Discussion	Our study independently replicated the associations of the ZNF804A SNPs rs7597593 and rs1344706 and…
16	Discussion	The mechanism underlying ZNF804A function in human brain and heroin addiction risk is not known.…
17	Discussion	Rs1344706 may also influence structure of addiction-relevant brain regions. In reporting the…
18	Discussion	Rs7597593 has also been implicated for influencing ZNF804A mRNA expression, but the association was…
19	Discussion	Our results support ZNF804A as one of the few susceptibility genes for heroin addiction with…

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Replication of ZNF804A gene variant associations with risk of heroin addiction.

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