Human Genetics

, 123:495

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

  • Yi Yu
  • Henry R. Kranzler
  • Carolien Panhuysen
  • Roger D. Weiss
  • James Poling
  • Lindsay A. Farrer
  • Joel Gelernter
Original Investigation


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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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Yi Yu
    • 1
  • Henry R. Kranzler
    • 4
  • Carolien Panhuysen
    • 1
    • 2
  • Roger D. Weiss
    • 5
  • James Poling
    • 6
  • Lindsay A. Farrer
    • 1
    • 2
    • 3
  • Joel Gelernter
    • 6
    • 7
  1. 1.Departments of Medicine (Genetics Program)Boston University Schools of Medicine and Public HealthBostonUSA
  2. 2.Departments of BiostatisticsBoston University Schools of Medicine and Public HealthBostonUSA
  3. 3.Departments of Neurology, Genetics and Genomics, EpidemiologyBoston University Schools of Medicine and Public HealthBostonUSA
  4. 4.Department of PsychiatryUniversity of Connecticut School of MedicineFarmingtonUSA
  5. 5.Department of Psychiatry, Harvard Medical SchoolAlcohol and Drug Abuse Treatment Program, McLean HospitalBostonUSA
  6. 6.Department of Psychiatry, Division of Human GeneticsYale University School of Medicine; and VA CT Healthcare CenterNew HavenUSA
  7. 7.Departments of Neurobiology and GeneticsYale University School of MedicineNew HavenUSA

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