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

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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.

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Acknowledgments

This work was supported by NIH (NIDA) grants R01 DA12690, R01 DA12849, K24 DA15105, K24 DA022288, and K24 AA013736. Dr. Kathleen Brady (Medical University of South Carolina) provided valuable patient recruitment and supervision at the MUSC site. We thank John Farrell for database management assistance. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University contract number N01-HG-65403.

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Authors and Affiliations

  1. Departments of Medicine (Genetics Program), Boston University Schools of Medicine and Public Health, Boston, MA, USA

    Yi Yu, Carolien Panhuysen & Lindsay A. Farrer

  2. Departments of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA

    Carolien Panhuysen & Lindsay A. Farrer

  3. Departments of Neurology, Genetics and Genomics, Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA

    Lindsay A. Farrer

  4. Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA

    Henry R. Kranzler

  5. Department of Psychiatry, Harvard Medical School, Alcohol and Drug Abuse Treatment Program, McLean Hospital, Boston, MA, USA

    Roger D. Weiss

  6. Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine; and VA CT Healthcare Center, New Haven, CT, USA

    James Poling & Joel Gelernter

  7. Departments of Neurobiology and Genetics, Yale University School of Medicine, New Haven, CT, USA

    Joel Gelernter

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  1. Yi Yu
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  2. Henry R. Kranzler
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  3. Carolien Panhuysen
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  4. Roger D. Weiss
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  6. Lindsay A. Farrer
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  7. Joel Gelernter
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Correspondence to Joel Gelernter.

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Yu, Y., Kranzler, H.R., Panhuysen, C. et al. Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet 123, 495–506 (2008). https://doi.org/10.1007/s00439-008-0501-0

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