@article{dc24b99a9089401190497def12750818,
title = "Linkage analysis followed by association show NRG1 associated with cannabis dependence in African Americans",
abstract = "Background: A genetic contribution to cannabis dependence (CaD) has been established but susceptibility genes for CaD remain largely unknown. Methods: We employed a multistage design to identify genetic variants underlying CaD. We first performed a genome-wide linkage scan for CaD in 384 African American (AA) and 354 European American families ascertained for genetic studies of cocaine and opioid dependence. We then conducted association analysis under the linkage peak, first using data from a genome-wide association study from the Study of Addiction: Genetics and Environment, followed by replication studies of prioritized single nucleotide polymorphisms (SNPs) in independent samples. Results: We identified the strongest linkage evidence with CaD (logarithm of odds = 2.9) on chromosome 8p21.1 in AAs. In the association analysis of the Study of Addiction: Genetics and Environment sample under the linkage peak, we identified one SNP (rs17664708) associated with CaD in both AAs (odds ratio [OR] = 2.93, p =.0022) and European Americans (OR = 1.38, p =.02). This SNP, located at NRG1, a susceptibility gene for schizophrenia, was prioritized for further study. We replicated the association of rs17664708 with CaD in an independent AAs sample (OR = 2.81, p =.0068). The joint analysis of the two AA samples demonstrated highly significant association between rs17664708 and CaD with adjustment for either global (p =.00044) or local ancestry (p =.00075). Conclusions: Our study shows that NRG1 is probably a susceptibility gene for CaD, based on convergent evidence of linkage and replicated associations in two independent AA samples.",
keywords = "Association, NRG1, SNP, candidate gene, cannabis dependence, linkage",
author = "Shizhong Han and Yang, {Bao Zhu} and Kranzler, {Henry R.} and David Oslin and Raymond Anton and Farrer, {Lindsay A.} and Joel Gelernter",
note = "Funding Information: This study was supported by National Institutes of Health (NIH) Grants R01 DA12690 , R01 DA12849 , RC2 DA028909 , R01 DA18432 , R01 AA11330 , R01 AA017535 , RO1 DA030976 , K01 DA24758 , and the Veterans Affairs (VA) Connecticut Reserve Educational Assistance Program center, a VA Merit Grant, VA National Center for Posttraumatic Stress Disorder Research, and the VA Connecticut and Veterans Integrated Service Network 4 Mental Illness Research, Education and Clinical Center Centers. It was also partially supported by the Alcoholic Beverage Medical Research Foundation Grant (SH). Funding Information: We are grateful to the volunteer families and individuals who participated in this research study. We gratefully acknowledge the assistance in recruitment and assessment provided at McLean Hospital by Roger Weiss, M.D., and at the Medical University of South Carolina by Kathleen Brady, M.D., Ph.D. Genotyping services of linkage analysis and our GWAS study were provided by the Center for Inherited Disease Research and Yale University (Keck Center). The Center for Inherited Disease Research is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number N01-HG-65403). We are grateful to Ann Marie Lacobelle, Michelle Cucinelli, Christa Robinson, and Greg Kay for their excellent technical assistance, to the Semi-Structured Assessment for Drug Dependence and Alcoholism interviewers who devoted substantial time and effort to phenotype the study sample, and to John Farrell for database management assistance. Funding Information: The datasets used for the analyses described in this manuscript were obtained from the database of Genotypes and Phenotypes at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1 through database of Genotypes and Phenotypes accession number phs000092.v1.p. Funding support for the Study of Addiction: Genetics and Environment was provided through the NIH Genes, Environment and Health Initiative ( U01 HG004422 ). The Study of Addiction: Genetics and Environment is one of the genome-wide association studies funded as part of the Gene Environment Association Studies under the Genes, Environment and Health Initiative. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the Gene Environment Association Studies Coordinating Center ( U01 HG004446 ). Funding Information: Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism ( U10 AA008401 ), the Collaborative Genetic Study of Nicotine Dependence ( P01 CA089392 ), and the Family Study of Cocaine Dependence ( R01 DA013423 ). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH Genes, Environment and Health Initiative ( U01HG004438 ), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” ( HHSN268200782096C ). ",
year = "2012",
month = oct,
day = "15",
doi = "10.1016/j.biopsych.2012.02.038",
language = "English (US)",
volume = "72",
pages = "637--644",
journal = "Biological psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "8",
}