title: Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene.
abstract: We report a genome-wide association study (GWAS) for cocaine dependence (CD) in three sets of African- and European-American subjects (AAs and EAs, respectively) to identify pathways, genes and alleles important in CD risk. The discovery GWAS data set (n=5697 subjects) was genotyped using the Illumina OmniQuad microarray (8 90 000 analyzed single-nucleotide polymorphisms (SNPs)). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4063 subjects. Then, the most significant GWAS SNPs were genotyped in 2549 independent subjects. We observed one genome-wide-significant (GWS) result: rs2629540 at the FAM53B ('family with sequence similarity 53, member B') locus. This was supported in both AAs and EAs; P-value (meta-analysis of all samples)=4.28 × 10(-8). The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 2) SNP rs150954431 was associated with P=1.19 × 10(-9) in the EA discovery sample. SNP rs2456778, which maps to CDK1 ('cyclin-dependent kinase 1'), was associated with cocaine-induced paranoia in AAs in the discovery sample only (P=4.68 × 10(-8)). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies.
authors: 1] Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [2] VA CT Healthcare Center, Department of Psychiatry, West Haven, CT, USA [3] Department of Genetics, Yale University School of Medicine, New Haven, CT, USA [4] Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
authors: J
authors: J
authors: Gelernter
authors: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors: R
authors: R
authors: Sherva
authors: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors: R
authors: R
authors: Koesterer
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: L
authors: L
authors: Almasy
authors: 1] Department of Genetics, Yale University School of Medicine, New Haven, CT, USA [2] Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.
authors: H
authors: H
authors: Zhao
authors: 1] Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA [2] Department of Psychiatry, Philadelphia VA Medical Center, Philadelphia, PA, USA.
authors: H R
authors: HR
authors: Kranzler
authors: 1] Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA [2] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [3] Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA [4] Department of Genetics and Genomics, Boston University School of Medicine, Boston, MA, USA [5] Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors: L
authors: L
authors: Farrer
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D016203:CDC2 Protein Kinase; D003042:Cocaine / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D056985:Nuclear Receptor Co-Repressor 2 / Q000235:genetics; D010259:Paranoid Disorders / Q000139:chemically induced / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D018765:Dopamine Uptake Inhibitors; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D003042:Cocaine
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