title: Neuronal calcium sensor-1 and cocaine addiction: a genetic association study in African-Americans and European Americans.
abstract: Genes involved in drug reward pathways are plausible candidates for susceptibility to substance use disorders. Given the prominent role of dopamine in drug reward, dopamine receptor-interacting proteins (DRIPs) such as the neuronal calcium sensor-1 (NCS-1) protein have been hypothesized to play a role in the pathophysiology of cocaine addiction (CA). In this study, we investigated whether genetic variants in the NCS-1 gene confer risk to CA. We genotyped 8 SNPs (rs4837479, rs7849345, rs3824544, rs10819611, rs947513, rs2277200, rs7873936 and rs1342043) in our discovery sample (cases n = 796, controls n = 416) of African descent. Confirmation of associated or trending SNPs (rs7849345, rs10819611, rs1342043) was attempted using a replication sample of African American (AA) ethnicity (cases n = 335, controls n = 336) and European-American (EA) ancestry (cases n = 336, controls n = 656). Secondary sex specific analysis was also carried out for each SNP in both AA and EA individuals. Genotyping of the discovery cohort showed significant genotypic (p = 0.0005, corrected q-value) as well as allelic (p = 0.005, corrected q-value) associations of rs1342043 with CA in AAs; however, this marker could not be confirmed in either the AA or EA replication sample. Combined analysis of all AA samples (n = 1883) for rs1342043 showed a significant association with CA (genotypic p = 0.0001, allelic p = 0.002) with a gender specific effect for males (allelic p = 0.005, genotypic p = 0.0003). Our data suggest that genetic variants in the NCS-1 gene contribute to susceptibility of CA in individuals of African descent.
authors.affiliation: Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, Department of Psychiatry, Philadelphia, PA, USA.
authors.forename: Pushpinder K
authors.initials: PK
authors.lastname: Multani
authors.forename: Toni-Kim
authors.initials: TK
authors.lastname: Clarke
authors.forename: Sneha
authors.initials: S
authors.lastname: Narasimhan
authors.forename: Lisa
authors.initials: L
authors.lastname: Ambrose-Lanci
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Kampman
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pettinati
authors.forename: David W
authors.initials: DW
authors.lastname: Oslin
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics* / Q000523:psychology; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012727:Sex Characteristics; D044465:White People / Q000235:genetics* / Q000523:psychology
chemical_list: D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins