Neuronal calcium sensor-1 and cocaine addiction: a genetic association study in African-Americans and European Americans.
- Authors
- Multani, Pushpinder K; Clarke, Toni-Kim; Narasimhan, Sneha; Ambrose-Lanci, Lisa; Kampman, Kyle M; Pettinati, Helen M; Oslin, David W; O'Brien, Charles P; Berrettini, Wade H; Lohoff, Falk W
- Year
- 2012
- Journal
- Neuroscience letters
- PMID
- 22999924
- DOI
- 10.1016/j.neulet.2012.09.014
- PMCID
- PMC3895491
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.
(A) Gene structure of NCS-1 and location of the genotyped SNPs in reference to the NCS-1 gene (http://genome.usc.edu) February 2009 (GRCh37/hg19) assembly. (B) Linkage disequilibrium (LD) between 8 SNPs genotyped in African Americans. (C) LD between 3 SNPs genotyped in European Americans. The shading represents r2 0.8 and numbers inside the boxes refer to ‘D’.
| Name | Type |
|---|---|
| AA | cohort |
| AA cocaine addicted individuals local | cohort |
| AA healthy controls local | cohort |
| AA males local | cohort |
| AA participants | cohort |
| AA population | cohort |
| AA population (TRC) local | cohort |
| abstinence | phenotype |
| addiction | phenotype |
| African American | cohort |
| alcohol dependence | phenotype |
| Both ethnicities local | cohort |
| calcium | drug |
| cocaine | phenotype |
| Cocaine-induced seizures local | phenotype |
| combined sample | cohort |
| COMT | gene |
| discovery sample | cohort |
| DRD2 | gene |
| DRD2-141Ins/Del local | variant |
| DRD3 | gene |
| DRD4 | gene |
| drug dependence | phenotype |
| EA | cohort |
| EA cases local | cohort |
| EA controls | cohort |
| EA participants | cohort |
| EA population | cohort |
| epilepsy | phenotype |
| European ancestry | cohort |
| GRK2 local | gene |
| HIV infection | phenotype |
| human abstinent cocaine abusers local | cohort |
| Male local | drug |
| National Institute of Mental Health Genetics Initiative control cohort local | cohort |
| NCS1 | gene |
| nicotine addiction | phenotype |
| nicotine dependence | phenotype |
| nicotine replacement therapy | drug |
| nucleus accumbens | anatomy |
| population | cohort |
| relapse | phenotype |
| replication sample | cohort |
| rs1054879 local | variant |
| rs10819611 local | variant |
| rs1342043 local | variant |
| rs2277200 local | variant |
| rs3824544 local | variant |
| rs4837479 local | variant |
| rs7849345 local | variant |
| rs7873936 local | variant |
| rs947513 local | variant |
| Rutgers replication sample local | cohort |
| Rutgers University Cell and DNA repository | cohort |
| sex | phenotype |
| SLC6A3 | gene |
| smoking cessation trial local | cohort |
| striatum | anatomy |
| substance use | phenotype |
| Thomas Jefferson University control cohort local | cohort |
| total AA population local | cohort |
| TRC local | cohort |
| TRC discovery sample local | cohort |
| University of Pennsylvania control cohort local | cohort |
| University of Pennsylvania Treatment Research Center (TRC) local | cohort |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene. | 2014 | 23958962 |
External
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|---|---|---|---|---|
| Nanomolar affinity of EF-hands in neuronal calcium sensor 1 for bivalent cations Pb2+, Mn2+, and Hg2. | Alam MS et al. | — | 2022 | → |
| Neuronal Calcium Sensor-1 Protects Cortical Neurons from Hyperexcitation and Ca<sup>2+</sup> Overload during Ischemia by Protecting the Population of GABAergic Neurons. | Varlamova EG et al. | — | 2022 | → |
| Comprehensive somatosensory and neurological phenotyping of NCS1 knockout mice. | Nguyen LD et al. | — | 2021 | → |
| Calcium Sensors in Neuronal Function and Dysfunction. | Burgoyne RD et al. | — | 2019 | → |
| Environmental, genetic and epigenetic contributions to cocaine addiction. | Pierce RC et al. | — | 2018 | → |
| NCS-1 is a regulator of calcium signaling in health and disease. | Boeckel GR et al. | — | 2018 | → |
| Genome-wide association study of treatment response to venlafaxine XR in generalized anxiety disorder. | Jung J et al. | — | 2017 | → |
| Possible Signaling Pathways Mediating Neuronal Calcium Sensor-1-Dependent Spatial Learning and Memory in Mice. | Nakamura TY et al. | — | 2017 | → |
| Identification of critical amino acid residues and functional conservation of the Neurospora crassa and Rattus norvegicus orthologues of neuronal calcium sensor-1. | Gohain D et al. | — | 2016 | → |
| Neuronal Calcium Sensor 1 Has Two Variants with Distinct Calcium Binding Characteristics. | Wang B et al. | — | 2016 | → |
| Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI. | Perrine SA et al. | — | 2015 | → |
| Self-directed exploration provides a Ncs1-dependent learning bonus. | Mun HS et al. | — | 2015 | → |
| Sense and specificity in neuronal calcium signalling. | Burgoyne RD et al. | — | 2015 | → |
| Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene. | Gelernter J et al. | — | 2014 | → |