Genome-wide linkage analysis of heroin dependence in Han Chinese: Results from Wave Two of a multi-stage study

Glatt, Stephen J.; Lasky‐Su, Jessica; Zhu, Shao C.; Zhang, Ruimin; Zhang, Bo; Li, Jixiang; Yuan, Xiaobo; Li, Jianhua; Lyons, Michael J.; Faraone, Stephen V.; Tsuang, Ming T.

doi:10.1016/j.drugalcdep.2008.04.011

Cited by 15 publications

(10 citation statements)

References 24 publications

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“…Members of the identified set of pedigrees were interviewed locally by trained interviewers with clinical experience (XYW, TQL, and WH) using the Chinese version of the Diagnostic Interview for Genetic Studies (DIGS 2.0; Berney et al 2002), to assess AD and related psychiatric phenotypes based on Diagnostic and Statistical Manual of Mental Disorders version IV (DSM-IV) criteria (American Psychiatric Association 2000). The DIGS was developed to ascertain psychiatric diagnoses including substance use disorders, and has been used for genetics studies of schizophrenia (Hwu et al 2005; Tang et al 2007) and heroin dependence (Glatt et al 2008) in Chinese samples.…”

Section: Methodsmentioning

confidence: 99%

ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample

Quillen

Chen

Almasy

et al. 2013

American J of Med Genetics Pt B

112

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Alcohol dependence (AD) is a moderately heritable phenotype with a small number of known risk genes mapped via linkage or candidate gene studies. We considered 313 males from among 600 members of documented, extended pedigrees in which AD segregates collected in Northern Hunan Province, China. A joint analysis of both males and females could not be performed as the difference in alcohol consumption variance was too large. Genome-wide association analyses were performed for approximately 300,000 single nucleotide polymorphisms (SNPs). Significant associations found in the ALDH2 region for AD (minimum p = 4.73×10-8) and two AD-related phenotypes: flushing response (minimum p = 4.75×10-26) and maximum drinks in a 24-hour period (minimum p = 1.54×10-16). Association of previous candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%, 7.9% and 22.9% of phenotypic variation, respectively, in this sample. When rs671 was considered as a candidate SNP in females, it explained 23.6% of the variation in flushing response, but alcohol consumption rates were too low among females – despite familial enrichment for AD – for an adequate test of association for either AD or maximum drinks. These results support a mediating effect of aldehyde dehydrogenase deficiency on alcohol consumption in males and a secondary, culturally-mediated limitation on alcohol consumption by females that should be appropriately modeled in future studies of alcohol consumption in populations where this may be a factor.

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Section: Methodsmentioning

confidence: 99%

ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample

Quillen

Chen

Almasy

et al. 2013

American J of Med Genetics Pt B

112

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“…Several linkage studies have provided evidence for the involvement of different chromosomal regions in the development of heroin addiction 260–262 . The Tsuang group studied Chinese families using short tandem repeat markers and found evidence for linkage for a region on chromosome 4 at D4S1644 with heroin dependence 263 .…”

Section: Genomewide and Multigene Association Studiesmentioning

confidence: 99%

Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment

Yuferov

Levran

Proudnikov

et al. 2010

Annals of the New York Academy of Sciences

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Addiction to opiates and illicit use of psychostimulants is a chronic, relapsing brain disease that, if left untreated, can cause major medical, social and economic problems. This article reviews recent progress in studies of association of gene variants with vulnerability to develop opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems. In addition, we provide the first evidence of a cis-acting polymorphism and a functional haplotype in the PDYN gene, of significantly higher DNA methylation rate of the OPRM1 gene in the lymphocytes of heroin addicts, and significant differences in genotype frequencies of three single nucleotide polymorphisms of the P-glycoprotein gene (ABCB1) between “higher” and “lower” methadone doses in methadone-maintained patients. In genome-wide and multi-gene association studies, we have found association of a number of new genes and new variants of known genes with heroin addiction. Finally, we have described the development and application of a novel technique: molecular haplotyping for studies in genetics of drug addiction.

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“…Several linkage studies suggest the involvement of specific chromosomal regions in the vulnerability to develop heroin addiction (Gelernter et al, 2006, Glatt et al, 2006, Glatt et al, 2008). The initial linkage study by the Tsuang group using 192 Chinese families and 386 short tandem repeat (STR) markers found a region on chromosome 4 at D4S1644 with evidence for linkage with heroin dependence (point-wise P = 0.014) (Glatt et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The initial linkage study by the Tsuang group using 192 Chinese families and 386 short tandem repeat (STR) markers found a region on chromosome 4 at D4S1644 with evidence for linkage with heroin dependence (point-wise P = 0.014) (Glatt et al, 2006). In their follow-up study, which included the original 192 families with a total of 397 Chinese families and 385 STR markers, the linkage signal on chromosome 4 at D4S1644 with greater significance (point-wise P = 0.004) (Glatt et al, 2008). Variant rs10518620, ranked seventh in Table 2 in our study and nominally associated with heroin addiction in the Caucasian group (point-wise P = 0.0003), is located between D4S1644 and the nearby marker D4S2394, which had nominal significance (point-wise P = 0.013) in the later Tsuang study.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction

Nielsen

Ji²,

Yuferov³

et al. 2010

Psychiatric Genetics

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Objectives We have used genome-wide association studies to identify variants that are associated with vulnerability to develop heroin addiction. Methods DNA from 325 methadone stabilized, former severe heroin addicts and 250 control subjects were pooled by ethnicity (Caucasian and African American) and analyzed using the Affymetrix GeneChip Mapping 100K Set. Genome-wide association tests were conducted. Results The strongest association with vulnerability to develop heroin addiction, with experiment-wise significance (P = 0.035), was found in Caucasians with the variant rs10494334, a variant in an unannotated region of the genome (1q23.3). In African Americans, the variant most significantly associated with heroin addiction vulnerability was rs950302, found in the cytosolic dual specificity phosphatase 27 gene DUSP27 (point-wise P = 0.0079). Furthermore, analysis of the top 500 variants with the most significant associations (point-wise P ≤ 0.0036) in Caucasians showed that three of these variants are clustered in the regulating synaptic membrane exocytosis protein 2 gene RIMS2. Of the top 500 variants in African Americans (point-wise P ≤ 0.0238), three variants are in the cardiomyopathy associated 3 gene CMYA3. Conclusions This study identifies new genes and variants that may increase an individual’s vulnerability to develop heroin addiction.

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Genome-wide linkage analysis of heroin dependence in Han Chinese: Results from Wave Two of a multi-stage study

Cited by 15 publications

References 24 publications

ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample

ALDH2 is associated to alcohol dependence and is the major genetic determinant of “daily maximum drinks” in a GWAS study of an isolated rural chinese sample

Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment

Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction

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