TY - JOUR
T1 - Association of superoxide dismutase 2 (SOD2) genotype with gray matter volume shrinkage in chronic alcohol users
T2 - Replication and further evaluation of an addiction gene panel
AU - Gitik, Miri
AU - Srivastava, Vibhuti
AU - Hodgkinson, Colin A.
AU - Shen, Pei Hong
AU - Goldman, David
AU - Meyerhoff, Dieter J.
N1 - Funding Information:
We thank the staff at the San Francisco VA Medical Center Substance Abuse Day Hospital and the Kaiser Permanente Chemical Dependency Recovery Program in San Francisco for their valuable assistance in recruiting participants. Our gratitude also goes to the study participants, who alone made this research possible. We also thank Dr. Yuan Qiaoping and Goli Yamini for their advice and contribution in generation and analysis of the custom genotyping array. This work was supported by grants from the National Institutes of Health (AA10788 and DA025202 to D.J.M.) administered by the Northern California Institute for Research and Education, and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center and also by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH.
PY - 2016/9
Y1 - 2016/9
N2 - Background: Reduction in brain volume, especially gray matter volume, has been shown to be one of the many deleterious effects of prolonged alcohol consumption. High variance in the degree of gray matter tissue shrinkage among alcohol dependent individuals and a previous neuroimaging genetics report suggest the involvement of environmental and/or genetic factors, such as superoxide dismutase 2 (SOD2). Identification of such underlying factors will help in the clinical management of alcohol dependence. Methods: We analyzed quantitative magnetic resonance imaging and genotype data from 103 alcohol users, including both light drinkers and treatment-seeking alcohol-dependent individuals. Genotyping was performed using a custom gene array that included genes selected from 8 pathways relevant to chronic alcohol-related brain volume loss. Results: We replicated a significant association of a functional SOD2 single nucleotide polymorphism with normalized gray matter volume, which had been reported previously in an independent smaller sample of alcohol-dependent individuals. The SOD2-related genetic protection was observed only at the cohort's lower drinking range. Additional associations between normalized gray matter volume and other candidate genes such as alcohol dehydrogenase gene cluster (ADH), GCLC, NOS3, and SYT1 were observed across the entire sample but did not survive corrections for multiple comparisons. Conclusion: Converging independent evidence for a SOD2 gene association with gray matter volume shrinkage in chronic alcohol users suggests that SOD2 genetic variants predict differential brain volume loss mediated by free radicals. This study also provides the first catalog of genetic variations relevant to gray matter loss in chronic alcohol users. The identified genebrain structure relationships are functionally pertinent and merit replication.
AB - Background: Reduction in brain volume, especially gray matter volume, has been shown to be one of the many deleterious effects of prolonged alcohol consumption. High variance in the degree of gray matter tissue shrinkage among alcohol dependent individuals and a previous neuroimaging genetics report suggest the involvement of environmental and/or genetic factors, such as superoxide dismutase 2 (SOD2). Identification of such underlying factors will help in the clinical management of alcohol dependence. Methods: We analyzed quantitative magnetic resonance imaging and genotype data from 103 alcohol users, including both light drinkers and treatment-seeking alcohol-dependent individuals. Genotyping was performed using a custom gene array that included genes selected from 8 pathways relevant to chronic alcohol-related brain volume loss. Results: We replicated a significant association of a functional SOD2 single nucleotide polymorphism with normalized gray matter volume, which had been reported previously in an independent smaller sample of alcohol-dependent individuals. The SOD2-related genetic protection was observed only at the cohort's lower drinking range. Additional associations between normalized gray matter volume and other candidate genes such as alcohol dehydrogenase gene cluster (ADH), GCLC, NOS3, and SYT1 were observed across the entire sample but did not survive corrections for multiple comparisons. Conclusion: Converging independent evidence for a SOD2 gene association with gray matter volume shrinkage in chronic alcohol users suggests that SOD2 genetic variants predict differential brain volume loss mediated by free radicals. This study also provides the first catalog of genetic variations relevant to gray matter loss in chronic alcohol users. The identified genebrain structure relationships are functionally pertinent and merit replication.
KW - Alcohol use disorder
KW - Genetics
KW - Gray matter volume
KW - Neuroimaging
KW - Superoxide dismutase 2 (SOD2)
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U2 - 10.1093/ijnp/pyw033
DO - 10.1093/ijnp/pyw033
M3 - Article
C2 - 27207918
AN - SCOPUS:84992225438
SN - 1461-1457
VL - 19
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
IS - 9
ER -