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Substance dependence low-density whole genome association study in two distinct American populations.

ABSTRACT: Cocaine and opioid dependence are common, complex disorders with high heritability that commonly co-occur with other substance dependence disorders. Improved insight into the genetic basis of substance dependence would help elucidate its etiology and could inform its prevention and treatment. To generate new hypotheses about the genetics of substance dependence, we genotyped 5633 tagging single nucleotide polymorphism (SNP) markers in 1699 subjects from 339 African American (AA) families and 334 European American (EA) families ascertained through a sib pair meeting DSM-IV criteria for either cocaine or opioid dependence. The associations between genetic markers and five substance dependence traits (cocaine dependence, opioid dependence, cocaine-induced paranoia, alcohol dependence, and nicotine dependence) were assessed by family based association tests (FBAT). Results were ranked according to several criteria including statistical significance, concordance of results across population samples, and potential biological relevance of the implicated gene. The top-ranked result was an association of SNP rs1133503 in the MANEA gene with cocaine-induced paranoia (CIP). Our study provides an initial substance dependence trait-specific blueprint of associated regions for future candidate gene studies.

SUBMITTER: Yu Y

PROVIDER: S-EPMC3428017 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Substance dependence low-density whole genome association study in two distinct American populations.

Yu Yi Y Kranzler Henry R HR Panhuysen Carolien C Weiss Roger D RD Poling James J Farrer Lindsay A LA Gelernter Joel J

Human genetics 20080426 5

Cocaine and opioid dependence are common, complex disorders with high heritability that commonly co-occur with other substance dependence disorders. Improved insight into the genetic basis of substance dependence would help elucidate its etiology and could inform its prevention and treatment. To generate new hypotheses about the genetics of substance dependence, we genotyped 5633 tagging single nucleotide polymorphism (SNP) markers in 1699 subjects from 339 African American (AA) families and 334 ...[more]

PMID: 18438686

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Project description:IntroductionSmoking prevalence, cigarettes per day (CPD), and lung cancer incidence differ between Northern Plains (NP) and Southwest (SW) American Indian populations. We used cotinine as a biomarker of tobacco smoke exposure to biochemically characterize NP and SW smokers and nonsmokers and to investigate factors associated with variation in tobacco exposure.MethodsAmerican Indians (N = 636) were recruited from two different tribal populations (NP and SW) as part of a study conducted as part of the Collaborative to Improve Native Cancer Outcomes P50 project. For each participant, a questionnaire assessed smoking status, CPD, second-hand smoke exposure, and traditional ceremonial tobacco use; plasma and/or salivary cotinine was measured.ResultsCotinine levels were (mean ± 95% confidence interval [CI]) 81.6 ± 14.1 and 21.3 ± 7.3 ng/ml among NP smokers and non-mokers, respectively, and 44.8 ± 14.4 and 9.8 ± 5.8 ng/ml among SW smokers and nonsmokers, respectively. Cotinine levels correlated with CPD in both populations (p < .0001). Cotinine ?15 ng/ml was measured in 73.4% of NP smokers and 47.8% of SW smokers and in 19.0% of NP nonsmokers and 10.9% of SW nonsmokers. Ceremonial traditional tobacco use was associated with higher cotinine among NP smokers only (p = 0.004). Second-hand smoke exposure was associated with higher cotinine among NP non-smokers (P < 0.02). More secondhand smoke exposure was associated with smoking more CPD in both populations (p = 0.03-0.29). Linear regression modeling mirrored these findings.ConclusionsHigh prevalence of smoking in the Northern Plains and high cotinine levels among nonsmokers in both regions highlights the tribal populations' risk for tobacco-related disease.ImplicationsThere is a high prevalence of smoking in Northern Plains American Indians. Among Northern Plains and Southwest nonsmokers, relatively high cotinine levels, representative of high tobacco exposure, suggest considerable exposure to second-hand smoke. It is critical to highlight the extent of second-hand smoke exposure among the Northern Plains and Southwest American Indians and to enhance efforts to initiate smoke-free policies in tribal communities, which are not subject to state-level polices.

Dataset Information

Substance dependence low-density whole genome association study in two distinct American populations.

Publications

Substance dependence low-density whole genome association study in two distinct American populations.

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