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The dopamine transporter gene SLC6A3: multidisease risks

Year: 2021
Type: article
Abstract: The human dopamine transporter gene SLC6A3 has been consistently implicated in several neuropsychiatric diseases but the disease mechanism remains elusive. In this risk synthesis, we have concluded that SLC6A3 represents an increasingly recognized risk with a growing number of familial mutants associated with neuropsychiatric and neurological disorders. At least five loci were related to common and severe diseases including alcohol use disorder (high activity variant), attention-deficit/hyperactivity disorder (low activity variant), autism (familial proteins with mutated networking) and movement disorders (both regulatory variants and familial mutations). Association signals depended on genetic markers used as well as ethnicity examined. Strong haplotype selection and gene-wide epistases support multimarker assessment of functional variations and phenotype associations. Inclusion of its promoter region's functional markers such as DNPi (rs67175440) and 5'VNTR (rs70957367) may help delineate condensate-based risk action, testing a locus-pathway-phenotype hypothesis for one gene-multidisease etiology.
DOI: 10.1038/s41380-021-01341-5
Authors: Maarten E. A. Reith, Sandhya Kortagere, Corinde E. Wiers, Hui Sun, Manju A. Kurian, Aurelio Galli, Nora D. Volkow, Zhicheng Lin
Institutions: New York University, Drexel University, National Institute on Alcohol Abuse and Alcoholism, University of Pennsylvania, Great Ormond Street Hospital, University College London, University of Alabama at Birmingham, National Institute on Drug Abuse, Harvard University, McLean Hospital
Language: English
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: U.S. Department of Health and Human Services, National Institute for Health and Care Research, Rosetrees Trust, Shanghai Jiao Tong University, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse
Awards: G1475995076, G1585308145, G1595541541, G1637912017, G1789530140, G1846436224, G2041825062, G2238475700, G2394293234, Human dopamine transporter gene: variation and transcriptional regulation, Modeling human alcohol abuse in mice with a common SLC6A3 regulatory variant, Understanding Genetic Causes of Cerebral Palsy: A Patient-Centric Approach to Improve Diagnosis and Develop New Treatments, G2734343, G3185291230, The dopamine transporter's lipid interactions: understanding transporter function, G3607473048, G4017098543, G4168694516, G4185700943, G493865823, G638003593, G641002866, G6412945130, G6445081585, Monitoring DAT in Live Rats, Biogenic Amine Transporters: Mechanisms of Ligand Interaction, G9000100347, G9000249426, G9000337923, The Role of the Dopamine Transporter in Psychostimulant Abuse, G988619686
OpenAlex ID: W3205605012
FWCI: 4.987
Cites: 150
Cited by: 113
Related to: 10